Daily Papers

ABACUS (Atomic-orbital Based Ab-initio Computation at USTC) is an open-source software for first-principles electronic structure calculations and molecular dynamics simulations. It mainly features density functional theory (DFT) and molecular dynamics functions and is compatible with both plane-wave basis sets and numerical atomic orbital basis sets. ABACUS serves as a platform that facilitates the integration of various electronic structure methods, such as Kohn-Sham DFT, stochastic DFT, orbital-free DFT, and real-time time-dependent DFT, etc. In addition, with the aid of high-performance computing, ABACUS is designed to perform efficiently and provide massive amounts of first-principles data for generating general-purpose machine learning potentials, such as DPA models. Furthermore, ABACUS serves as an electronic structure platform that interfaces with several AI-assisted algorithms and packages, such as DeePKS-kit, DeePMD, DP-GEN, DeepH, DeePTB, HamGNN, etc.

Recent neural network-based wave functions have achieved state-of-the-art accuracies in modeling ab-initio ground-state potential energy surface. However, these networks can only solve different spatial arrangements of the same set of atoms. To overcome this limitation, we present Graph-learned orbital embeddings (Globe), a neural network-based reparametrization method that can adapt neural wave functions to different molecules. Globe learns representations of local electronic structures that generalize across molecules via spatial message passing by connecting molecular orbitals to covalent bonds. Further, we propose a size-consistent wave function Ansatz, the Molecular orbital network (Moon), tailored to jointly solve Schr\"odinger equations of different molecules. In our experiments, we find Moon converging in 4.5 times fewer steps to similar accuracy as previous methods or to lower energies given the same time. Further, our analysis shows that Moon's energy estimate scales additively with increased system sizes, unlike previous work where we observe divergence. In both computational chemistry and machine learning, we are the first to demonstrate that a single wave function can solve the Schr\"odinger equation of molecules with different atoms jointly.

Slater-type orbitals (STOs) provide the physically correct description of atomic wavefunctions but have been largely replaced by Gaussian-type orbitals in computational chemistry due to the lack of closed-form multi-center integrals. We present a systematic study of amplitude encoding of STOs on quantum computers using matrix product states (MPS). For one-dimensional orbital functions of the form p_d(x) e^{-ζx}, we derive analytical MPS constructions with constant bond dimension χ= d + 1, requiring O(n) classical and quantum resources for n-qubit registers with no grid sampling. We demonstrate a complete one-electron integral pipeline -- overlap, kinetic energy, and nuclear attraction -- in one dimension, validating the overlap and kinetic energy on IBM Heron processors at 5~qubits with 0.67\% hardware-induced error using Zero-Noise Extrapolation. In three dimensions, we compute multi-center overlap integrals between 1s and 2s orbitals in Cartesian coordinates with 0.02\% discretization error at 18~qubits. A systematic entanglement analysis reveals that the MPS bond dimension of three-dimensional STOs in Cartesian coordinates saturates with increasing grid resolution -- reaching sim138 for the hydrogen 1s orbital at 12~qubits per coordinate -- establishing bounded encoding complexity rather than the exponential scaling initially expected. The SVD truncation threshold provides a practical resource parameter, reducing the bond dimension to 39 at threshold 10^{-6} with negligible accuracy loss. These results map the entanglement landscape for amplitude encoding of atomic orbitals and establish MPS-based state preparation as a viable path toward exact STO basis sets on quantum computers.

The combination of modern scientific computing with electronic structure theory can lead to an unprecedented amount of data amenable to intelligent data analysis for the identification of meaningful, novel, and predictive structure-property relationships. Such relationships enable high-throughput screening for relevant properties in an exponentially growing pool of virtual compounds that are synthetically accessible. Here, we present a machine learning (ML) model, trained on a data base of ab initio calculation results for thousands of organic molecules, that simultaneously predicts multiple electronic ground- and excited-state properties. The properties include atomization energy, polarizability, frontier orbital eigenvalues, ionization potential, electron affinity, and excitation energies. The ML model is based on a deep multi-task artificial neural network, exploiting underlying correlations between various molecular properties. The input is identical to ab initio methods, i.e. nuclear charges and Cartesian coordinates of all atoms. For small organic molecules the accuracy of such a "Quantum Machine" is similar, and sometimes superior, to modern quantum-chemical methods---at negligible computational cost.

Methods of computational quantum chemistry provide accurate approximations of molecular properties crucial for computer-aided drug discovery and other areas of chemical science. However, high computational complexity limits the scalability of their applications. Neural network potentials (NNPs) are a promising alternative to quantum chemistry methods, but they require large and diverse datasets for training. This work presents a new dataset and benchmark called nabla^2DFT that is based on the nablaDFT. It contains twice as much molecular structures, three times more conformations, new data types and tasks, and state-of-the-art models. The dataset includes energies, forces, 17 molecular properties, Hamiltonian and overlap matrices, and a wavefunction object. All calculations were performed at the DFT level (omegaB97X-D/def2-SVP) for each conformation. Moreover, nabla^2DFT is the first dataset that contains relaxation trajectories for a substantial number of drug-like molecules. We also introduce a novel benchmark for evaluating NNPs in molecular property prediction, Hamiltonian prediction, and conformational optimization tasks. Finally, we propose an extendable framework for training NNPs and implement 10 models within it.

Recently, sophisticated deep learning-based approaches have been developed for generating efficient initial guesses to accelerate the convergence of density functional theory (DFT) calculations. While the actual initial guesses are often density matrices (DM), quantities that can convert into density matrices also qualify as alternative forms of initial guesses. Hence, existing works mostly rely on the prediction of the Hamiltonian matrix for obtaining high-quality initial guesses. However, the Hamiltonian matrix is both numerically difficult to predict and intrinsically non-transferable, hindering the application of such models in real scenarios. In light of this, we propose a method that constructs DFT initial guesses by predicting the electron density in a compact auxiliary basis representation using E(3)-equivariant neural networks. Trained on small molecules with up to 20 atoms, our model is able to achieve an average 33.3% self-consistent field (SCF) step reduction on systems up to 60 atoms, substantially outperforming Hamiltonian-centric and DM-centric models. Critically, this acceleration remains nearly constant with increasing system sizes and exhibits strong transferring behaviors across orbital basis sets and exchange-correlation (XC) functionals. To the best of our knowledge, this work represents the first and robust candidate for a universally transferable DFT acceleration method. We are also releasing the SCFbench dataset and its accompanying code to facilitate future research in this promising direction.

Chemically accurate and comprehensive studies of the virtual space of all possible molecules are severely limited by the computational cost of quantum chemistry. We introduce a composite strategy that adds machine learning corrections to computationally inexpensive approximate legacy quantum methods. After training, highly accurate predictions of enthalpies, free energies, entropies, and electron correlation energies are possible, for significantly larger molecular sets than used for training. For thermochemical properties of up to 16k constitutional isomers of C_7H_{10}O_2 we present numerical evidence that chemical accuracy can be reached. We also predict electron correlation energy in post Hartree-Fock methods, at the computational cost of Hartree-Fock, and we establish a qualitative relationship between molecular entropy and electron correlation. The transferability of our approach is demonstrated, using semi-empirical quantum chemistry and machine learning models trained on 1 and 10\% of 134k organic molecules, to reproduce enthalpies of all remaining molecules at density functional theory level of accuracy.

This work describes the theoretical foundation for all quantum chemistry functionality in PennyLane, a quantum computing software library specializing in quantum differentiable programming. We provide an overview of fundamental concepts in quantum chemistry, including the basic principles of the Hartree-Fock method. A flagship feature in PennyLane is the differentiable Hartree-Fock solver, allowing users to compute exact gradients of molecular Hamiltonians with respect to nuclear coordinates and basis set parameters. PennyLane provides specialized operations for quantum chemistry, including excitation gates as Givens rotations and templates for quantum chemistry circuits. Moreover, built-in simulators exploit sparse matrix techniques for representing molecular Hamiltonians that lead to fast simulation for quantum chemistry applications. In combination with PennyLane's existing methods for constructing, optimizing, and executing circuits, these methods allow users to implement a wide range of quantum algorithms for quantum chemistry. We discuss how PennyLane can be used to implement variational algorithms for calculating ground-state energies, excited-state energies, and energy derivatives, all of which can be differentiated with respect to both circuit and Hamiltonian parameters. We provide an example workflow describing how to jointly optimize circuit parameters, nuclear coordinates, and basis set parameters for quantum chemistry algorithms. We discuss a functionality for reducing the number of qubits by using symmetries and explain how PennyLane can be used to estimate quantum resources needed to implement several quantum algorithms. By combining insights from quantum computing, computational chemistry, and machine learning, PennyLane is the first library for differentiable quantum computational chemistry.

We present the design of a flexible quantum-chemical method development framework, which supports employing any type of basis function. This design has been implemented in the light-weight program package molsturm, yielding a basis-function-independent self-consistent field scheme. Versatile interfaces, making use of open standards like python, mediate the integration of molsturm with existing third-party packages. In this way both rapid extension of the present set of methods for electronic structure calculations as well as adding new basis function types can be readily achieved. This makes molsturm well-suitable for testing novel approaches for discretising the electronic wave function and allows comparing them to existing methods using the same software stack. This is illustrated by two examples, an implementation of coupled-cluster doubles as well as a gradient-free geometry optimisation, where in both cases, an arbitrary basis functions could be used. molsturm is open-source and can be obtained from https://molsturm.org.

We introduce featom, an open source code that implements a high-order finite element solver for the radial Schr\"odinger, Dirac, and Kohn-Sham equations. The formulation accommodates various mesh types, such as uniform or exponential, and the convergence can be systematically controlled by increasing the number and/or polynomial order of the finite element basis functions. The Dirac equation is solved using a squared Hamiltonian approach to eliminate spurious states. To address the slow convergence of the kappa=pm1 states due to divergent derivatives at the origin, we incorporate known asymptotic forms into the solutions. We achieve a high level of accuracy (10^{-8} Hartree) for total energies and eigenvalues of heavy atoms such as uranium in both Schr\"odinger and Dirac Kohn-Sham solutions. We provide detailed convergence studies and computational parameters required to attain commonly required accuracies. Finally, we compare our results with known analytic results as well as the results of other methods. In particular, we calculate benchmark results for atomic numbers (Z) from 1 to 92, verifying current benchmarks. We demonstrate significant speedup compared to the state-of-the-art shooting solver dftatom. An efficient, modular Fortran 2008 implementation, is provided under an open source, permissive license, including examples and tests, wherein particular emphasis is placed on the independence (no global variables), reusability, and generality of the individual routines.

Supervised machine learning approaches have been increasingly used in accelerating electronic structure prediction as surrogates of first-principle computational methods, such as density functional theory (DFT). While numerous quantum chemistry datasets focus on chemical properties and atomic forces, the ability to achieve accurate and efficient prediction of the Hamiltonian matrix is highly desired, as it is the most important and fundamental physical quantity that determines the quantum states of physical systems and chemical properties. In this work, we generate a new Quantum Hamiltonian dataset, named as QH9, to provide precise Hamiltonian matrices for 999 or 2998 molecular dynamics trajectories and 130,831 stable molecular geometries, based on the QM9 dataset. By designing benchmark tasks with various molecules, we show that current machine learning models have the capacity to predict Hamiltonian matrices for arbitrary molecules. Both the QH9 dataset and the baseline models are provided to the community through an open-source benchmark, which can be highly valuable for developing machine learning methods and accelerating molecular and materials design for scientific and technological applications. Our benchmark is publicly available at https://github.com/divelab/AIRS/tree/main/OpenDFT/QHBench.

Graph neural networks are emerging as promising methods for modeling molecular graphs, in which nodes and edges correspond to atoms and chemical bonds, respectively. Recent studies show that when 3D molecular geometries, such as bond lengths and angles, are available, molecular property prediction tasks can be made more accurate. However, computing of 3D molecular geometries requires quantum calculations that are computationally prohibitive. For example, accurate calculation of 3D geometries of a small molecule requires hours of computing time using density functional theory (DFT). Here, we propose to predict the ground-state 3D geometries from molecular graphs using machine learning methods. To make this feasible, we develop a benchmark, known as Molecule3D, that includes a dataset with precise ground-state geometries of approximately 4 million molecules derived from DFT. We also provide a set of software tools for data processing, splitting, training, and evaluation, etc. Specifically, we propose to assess the error and validity of predicted geometries using four metrics. We implement two baseline methods that either predict the pairwise distance between atoms or atom coordinates in 3D space. Experimental results show that, compared with generating 3D geometries with RDKit, our method can achieve comparable prediction accuracy but with much smaller computational costs. Our Molecule3D is available as a module of the MoleculeX software library (https://github.com/divelab/MoleculeX).

We develop a framework for on-the-fly machine learned force field molecular dynamics simulations based on the multipole featurization scheme that overcomes the bottleneck with the number of chemical elements. Considering bulk systems with up to 6 elements, we demonstrate that the number of density functional theory calls remains approximately independent of the number of chemical elements, in contrast to the increase in the smooth overlap of atomic positions scheme.

We present OrbNet Denali, a machine learning model for electronic structure that is designed as a drop-in replacement for ground-state density functional theory (DFT) energy calculations. The model is a message-passing neural network that uses symmetry-adapted atomic orbital features from a low-cost quantum calculation to predict the energy of a molecule. OrbNet Denali is trained on a vast dataset of 2.3 million DFT calculations on molecules and geometries. This dataset covers the most common elements in bio- and organic chemistry (H, Li, B, C, N, O, F, Na, Mg, Si, P, S, Cl, K, Ca, Br, I) as well as charged molecules. OrbNet Denali is demonstrated on several well-established benchmark datasets, and we find that it provides accuracy that is on par with modern DFT methods while offering a speedup of up to three orders of magnitude. For the GMTKN55 benchmark set, OrbNet Denali achieves WTMAD-1 and WTMAD-2 scores of 7.19 and 9.84, on par with modern DFT functionals. For several GMTKN55 subsets, which contain chemical problems that are not present in the training set, OrbNet Denali produces a mean absolute error comparable to those of DFT methods. For the Hutchison conformers benchmark set, OrbNet Denali has a median correlation coefficient of R^2=0.90 compared to the reference DLPNO-CCSD(T) calculation, and R^2=0.97 compared to the method used to generate the training data (wB97X-D3/def2-TZVP), exceeding the performance of any other method with a similar cost. Similarly, the model reaches chemical accuracy for non-covalent interactions in the S66x10 dataset. For torsional profiles, OrbNet Denali reproduces the torsion profiles of wB97X-D3/def2-TZVP with an average MAE of 0.12 kcal/mol for the potential energy surfaces of the diverse fragments in the TorsionNet500 dataset.

Material representations that are compatible with machine learning models play a key role in developing models that exhibit high accuracy for property prediction. Atomic orbital interactions are one of the important factors that govern the properties of crystalline materials, from which the local chemical environments of atoms is inferred. Therefore, to develop robust machine learningmodels for material properties prediction, it is imperative to include features representing such chemical attributes. Here, we propose the Orbital Graph Convolutional Neural Network (OGCNN), a crystal graph convolutional neural network framework that includes atomic orbital interaction features that learns material properties in a robust way. In addition, we embedded an encoder-decoder network into the OGCNN enabling it to learn important features among basic atomic (elemental features), orbital-orbital interactions, and topological features. We examined the performance of this model on a broad range of crystalline material data to predict different properties. We benchmarked the performance of the OGCNN model with that of: 1) the crystal graph convolutional neural network (CGCNN), 2) other state-of-the-art descriptors for material representations including Many-body Tensor Representation (MBTR) and the Smooth Overlap of Atomic Positions (SOAP), and 3) other conventional regression machine learning algorithms where different crystal featurization methods have been used. We find that OGCNN significantly outperforms them. The OGCNN model with high predictive accuracy can be used to discover new materials among the immense phase and compound spaces of materials

Parameterized tight-binding models fit to first principles calculations can provide an efficient and accurate quantum mechanical method for predicting properties of molecules and solids. However, well-tested parameter sets are generally only available for a limited number of atom combinations, making routine use of this method difficult. Furthermore, most previous models consider only simple two-body interactions, which limits accuracy. To tackle these challenges, we develop a density functional theory database of nearly one million materials, which we use to fit a universal set of tight-binding parameters for 65 elements and their binary combinations. We include both two-body and three-body effective interaction terms in our model, plus self-consistent charge transfer, enabling our model to work for metallic, covalent, and ionic bonds with the same parameter set. To ensure predictive power, we adopt a learning framework where we repeatedly test the model on new low energy crystal structures and then add them to the fitting dataset, iterating until predictions improve. We distribute the materials database and tools developed in this work publicly.

Machine-learning generative methods for material design are constructed by representing a given chemical structure, either a solid or a molecule, over appropriate atomic features, generally called structural descriptors. These must be fully descriptive of the system, must facilitate the training process and must be invertible, so that one can extract the atomic configurations corresponding to the output of the model. In general, this last requirement is not automatically satisfied by the most efficient structural descriptors, namely the representation is not directly invertible. Such drawback severely limits our freedom of choice in selecting the most appropriate descriptors for the problem, and thus our flexibility to construct generative models. In this work, we present a general optimization method capable of inverting any local many-body descriptor of the chemical environment, back to a cartesian representation. The algorithm is then implemented together with the bispectrum representation of the local structure and demonstrated for a number of molecules. The scheme presented here, thus, represents a general approach to the inversion of structural descriptors, enabling the construction of efficient structural generative models.

Orbital-free density functional theory (OF-DFT) holds the promise to compute ground state molecular properties at minimal cost. However, it has been held back by our inability to compute the kinetic energy as a functional of the electron density only. We here set out to learn the kinetic energy functional from ground truth provided by the more expensive Kohn-Sham density functional theory. Such learning is confronted with two key challenges: Giving the model sufficient expressivity and spatial context while limiting the memory footprint to afford computations on a GPU; and creating a sufficiently broad distribution of training data to enable iterative density optimization even when starting from a poor initial guess. In response, we introduce KineticNet, an equivariant deep neural network architecture based on point convolutions adapted to the prediction of quantities on molecular quadrature grids. Important contributions include convolution filters with sufficient spatial resolution in the vicinity of the nuclear cusp, an atom-centric sparse but expressive architecture that relays information across multiple bond lengths; and a new strategy to generate varied training data by finding ground state densities in the face of perturbations by a random external potential. KineticNet achieves, for the first time, chemical accuracy of the learned functionals across input densities and geometries of tiny molecules. For two electron systems, we additionally demonstrate OF-DFT density optimization with chemical accuracy.

Developing robust representations of chemical structures that enable models to learn topological inductive biases is challenging. In this manuscript, we present a representation of atomistic systems. We begin by proving that our representation satisfies all structural, geometric, efficiency, and generalizability constraints. Afterward, we provide a general algorithm to encode any atomistic system. Finally, we report performance comparable to state-of-the-art methods on numerous tasks. We open-source all code and datasets. The code and data are available at https://github.com/rahulkhorana/PolyatomicComplexes.

Classical force fields (FF) based on machine learning (ML) methods show great potential for large scale simulations of materials. MLFFs have hitherto largely been designed and fitted for specific systems and are not usually transferable to chemistries beyond the specific training set. We develop a unified atomisitic line graph neural network-based FF (ALIGNN-FF) that can model both structurally and chemically diverse materials with any combination of 89 elements from the periodic table. To train the ALIGNN-FF model, we use the JARVIS-DFT dataset which contains around 75000 materials and 4 million energy-force entries, out of which 307113 are used in the training. We demonstrate the applicability of this method for fast optimization of atomic structures in the crystallography open database and by predicting accurate crystal structures using genetic algorithm for alloys.

Merging first-principles calculations with machine learning (ML), we aim to accelerate the exploration of catalytic behaviour in novel materials. We focus on two-dimensional (2D) Ti_2CT_y MXenes, whose versatile surface chemistry makes them particularly compelling candidates for catalysis. Resolving their composition and structure under realistic conditions exceeds the reach of standard density functional theory (DFT) due to computational cost. To address this challenge, we generate a comprehensive dataset of 50,000 DFT calculations for training and 10,000 for testing, encompassing both Ti_2CT_y MXene configurations and molecular systems, along with an additional test dataset with 1000 genuinely new, larger systems to investigate how well models generalise. We train and validate widely used and competitive machine learning interatomic potential (MLIP) models, including EquiformerV2, MACE, MatRIS, and UPET, that accurately predict atomic forces and formation energies -- quantities that DFT must repeatedly compute for structural and catalytic investigations -- for these 2D materials. This combined DFT-ML framework achieves computational acceleration on the order of approximately 1-4 cdot 10^3 (on a CPU) while maintaining desired-level accuracy (approximately +/- 10 meV/A for forces and approximately +/- 1 meV for per-atom energies), paving the way for more efficient investigations of MXene catalytic behaviour. Moreover, we perform an extensive qualitative evaluation of the trained models, showcasing the importance of comprehensive simulation-based comparison beyond benchmark metrics. The dataset and the trained models with the code are available at https://huggingface.co/datasets/CatalystAnonymous/catalyst_mxenes.

We present developments and applications for the diagonalization of shell-model hamiltonians in a discrete non-orthogonal basis (DNO-SM). The method, and its actual numerical implementation CARINA, based on mean-field and beyond-mean field techniques has already been applied in previous studies and is focused on basis states selection optimization. The method is benchmarked against a full set of sd shell exact diagonalizations, and is applied for the first time to the heavy deformed ^{254}No nucleus.

Density functional theory (DFT) stands as a cornerstone method in computational quantum chemistry and materials science due to its remarkable versatility and scalability. Yet, it suffers from limitations in accuracy, particularly when dealing with strongly correlated systems. To address these shortcomings, recent work has begun to explore how machine learning can expand the capabilities of DFT; an endeavor with many open questions and technical challenges. In this work, we present Grad DFT: a fully differentiable JAX-based DFT library, enabling quick prototyping and experimentation with machine learning-enhanced exchange-correlation energy functionals. Grad DFT employs a pioneering parametrization of exchange-correlation functionals constructed using a weighted sum of energy densities, where the weights are determined using neural networks. Moreover, Grad DFT encompasses a comprehensive suite of auxiliary functions, notably featuring a just-in-time compilable and fully differentiable self-consistent iterative procedure. To support training and benchmarking efforts, we additionally compile a curated dataset of experimental dissociation energies of dimers, half of which contain transition metal atoms characterized by strong electronic correlations. The software library is tested against experimental results to study the generalization capabilities of a neural functional across potential energy surfaces and atomic species, as well as the effect of training data noise on the resulting model accuracy.

The reliability with Machine Learning (ML) techniques in novel materials discovery often depend on the quality of the dataset, in addition to the relevant features used in describing the material. In this regard, the current study presents and validates a newly processed materials dataset that can be utilized for benchmark ML analysis, as it relates to the prediction and classification of deterministic target properties. Originally, the dataset was extracted from the Open Quantum Materials Database (OQMD) and contains a robust 16,323 samples of ABX3 inorganic perovskite structures. The dataset is tabular in form and is preprocessed to include sixty-one generalized input features that broadly describes the physicochemical, stability/geometrical, and Density Functional Theory (DFT) target properties associated with the elemental ionic sites in a three-dimensional ABX3 polyhedral. For validation, four different ML models are employed to predict three distinctive target properties, namely: formation energy, energy band gap, and crystal system. On experimentation, the best accuracy measurements are reported at 0.013 eV/atom MAE, 0.216 eV MAE, and 85% F1, corresponding to the formation energy prediction, band gap prediction and crystal system multi-classification, respectively. Moreover, the realized results are compared with previous literature and as such, affirms the resourcefulness of the current dataset for future benchmark materials analysis via ML techniques. The preprocessed dataset and source codes are openly available to download from github.com/chenebuah/ML_abx3_dataset.

Machine learning potentials are an important tool for molecular simulation, but their development is held back by a shortage of high quality datasets to train them on. We describe the SPICE dataset, a new quantum chemistry dataset for training potentials relevant to simulating drug-like small molecules interacting with proteins. It contains over 1.1 million conformations for a diverse set of small molecules, dimers, dipeptides, and solvated amino acids. It includes 15 elements, charged and uncharged molecules, and a wide range of covalent and non-covalent interactions. It provides both forces and energies calculated at the ωB97M-D3(BJ)/def2-TZVPPD level of theory, along with other useful quantities such as multipole moments and bond orders. We train a set of machine learning potentials on it and demonstrate that they can achieve chemical accuracy across a broad region of chemical space. It can serve as a valuable resource for the creation of transferable, ready to use potential functions for use in molecular simulations.

Machine learning potentials (MLPs) trained on accurate quantum chemical data can retain the high accuracy, while inflicting little computational demands. On the downside, they need to be trained for each individual system. In recent years, a vast number of MLPs has been trained from scratch because learning additional data typically requires to train again on all data to not forget previously acquired knowledge. Additionally, most common structural descriptors of MLPs cannot represent efficiently a large number of different chemical elements. In this work, we tackle these problems by introducing element-embracing atom-centered symmetry functions (eeACSFs) which combine structural properties and element information from the periodic table. These eeACSFs are a key for our development of a lifelong machine learning potential (lMLP). Uncertainty quantification can be exploited to transgress a fixed, pre-trained MLP to arrive at a continuously adapting lMLP, because a predefined level of accuracy can be ensured. To extend the applicability of an lMLP to new systems, we apply continual learning strategies to enable autonomous and on-the-fly training on a continuous stream of new data. For the training of deep neural networks, we propose the continual resilient (CoRe) optimizer and incremental learning strategies relying on rehearsal of data, regularization of parameters, and the architecture of the model.

Accurately modeling chemical reactions at the atomistic level requires high-level electronic structure theory due to the presence of unpaired electrons and the need to properly describe bond breaking and making energetics. Commonly used approaches such as Density Functional Theory (DFT) frequently fail for this task due to deficiencies that are well recognized. However, for high-fidelity approaches, creating large datasets of energies and forces for reactive processes to train machine learning interatomic potentials or force fields is daunting. For example, the use of the unrestricted coupled cluster level of theory has previously been seen as unfeasible due to high computational costs, the lack of analytical gradients in many computational codes, and additional challenges such as constructing suitable basis set corrections for forces. In this work, we develop new methods and workflows to overcome the challenges inherent to automating unrestricted coupled cluster calculations. Using these advancements, we create a dataset of gas-phase reactions containing energies and forces for 3119 different organic molecules configurations calculated at the gold-standard level of unrestricted CCSD(T) (coupled cluster singles doubles and perturbative triples). With this dataset, we provide an analysis of the differences between the density functional and unrestricted CCSD(T) descriptions. We develop a transferable machine learning interatomic potential for gas-phase reactions, trained on unrestricted CCSD(T) data, and demonstrate the advantages of transitioning away from DFT data. Transitioning from training to DFT to training to UCCSD(T) datasets yields an improvement of more than 0.1 eV/Å in force accuracy and over 0.1 eV in activation energy reproduction.

Machine learning techniques are essential tools to compute efficient, yet accurate, force fields for atomistic simulations. This approach has recently been extended to incorporate quantum computational methods, making use of variational quantum learning models to predict potential energy surfaces and atomic forces from ab initio training data. However, the trainability and scalability of such models are still limited, due to both theoretical and practical barriers. Inspired by recent developments in geometric classical and quantum machine learning, here we design quantum neural networks that explicitly incorporate, as a data-inspired prior, an extensive set of physically relevant symmetries. We find that our invariant quantum learning models outperform their more generic counterparts on individual molecules of growing complexity. Furthermore, we study a water dimer as a minimal example of a system with multiple components, showcasing the versatility of our proposed approach and opening the way towards larger simulations. Our results suggest that molecular force fields generation can significantly profit from leveraging the framework of geometric quantum machine learning, and that chemical systems represent, in fact, an interesting and rich playground for the development and application of advanced quantum machine learning tools.

Computational high-throughput virtual screening is essential for identifying redox-active molecules for sustainable applications such as electrochemical carbon capture. A primary challenge in this approach is the high computational cost associated with accurate quantum chemistry calculations. Machine learning foundation potentials (FPs) trained on extensive density functional theory (DFT) calculations offer a computationally efficient alternative. Here, we benchmark the MACE-OMol-0 and UMA FPs against a hierarchy of DFT functionals for predicting experimental molecular redox potentials for both electron transfer (ET) and proton-coupled electron transfer (PCET) reactions. We find that these FPs achieve exceptional accuracy for PCET processes, rivaling their target DFT method. However, the performance is diminished for ET reactions, particularly for multi-electron transfers involving reactive ions that are underrepresented in the OMol25 training data, revealing a key out-of-distribution limitation. To overcome this, we propose an optimal hybrid workflow that uses the FPs for efficient geometry optimization and thermochemical analysis, followed by a crucial single-point DFT energy refinement and an implicit solvation correction. This pragmatic approach provides a robust and scalable strategy for accelerating high-throughput virtual screening in sustainable chemistry.

We pursue the development and application of the recently-introduced linear optimization method for determining the optimal linear and nonlinear parameters of Jastrow-Slater wave functions in a variational Monte Carlo framework. In this approach, the optimal parameters are found iteratively by diagonalizing the Hamiltonian matrix in the space spanned by the wave function and its first-order derivatives, making use of a strong zero-variance principle. We extend the method to optimize the exponents of the basis functions, simultaneously with all the other parameters, namely the Jastrow, configuration state function and orbital parameters. We show that the linear optimization method can be thought of as a so-called augmented Hessian approach, which helps explain the robustness of the method and permits us to extend it to minimize a linear combination of the energy and the energy variance. We apply the linear optimization method to obtain the complete ground-state potential energy curve of the C_2 molecule up to the dissociation limit, and discuss size consistency and broken spin-symmetry issues in quantum Monte Carlo calculations. We perform calculations of the first-row atoms and homonuclear diatomic molecules with fully optimized Jastrow-Slater wave functions, and we demonstrate that molecular well depths can be obtained with near chemical accuracy quite systematically at the diffusion Monte Carlo level for these systems.

Modeling the energy and forces of atomic systems is a fundamental problem in computational chemistry with the potential to help address many of the world's most pressing problems, including those related to energy scarcity and climate change. These calculations are traditionally performed using Density Functional Theory, which is computationally very expensive. Machine learning has the potential to dramatically improve the efficiency of these calculations from days or hours to seconds. We propose the Spherical Channel Network (SCN) to model atomic energies and forces. The SCN is a graph neural network where nodes represent atoms and edges their neighboring atoms. The atom embeddings are a set of spherical functions, called spherical channels, represented using spherical harmonics. We demonstrate, that by rotating the embeddings based on the 3D edge orientation, more information may be utilized while maintaining the rotational equivariance of the messages. While equivariance is a desirable property, we find that by relaxing this constraint in both message passing and aggregation, improved accuracy may be achieved. We demonstrate state-of-the-art results on the large-scale Open Catalyst dataset in both energy and force prediction for numerous tasks and metrics.

We introduce the FCHL19 representation for atomic environments in molecules or condensed-phase systems. Machine learning models based on FCHL19 are able to yield predictions of atomic forces and energies of query compounds with chemical accuracy on the scale of milliseconds. FCHL19 is a revision of our previous work [Faber et al. 2018] where the representation is discretized and the individual features are rigorously optimized using Monte Carlo optimization. Combined with a Gaussian kernel function that incorporates elemental screening, chemical accuracy is reached for energy learning on the QM7b and QM9 datasets after training for minutes and hours, respectively. The model also shows good performance for non-bonded interactions in the condensed phase for a set of water clusters with an MAE binding energy error of less than 0.1 kcal/mol/molecule after training on 3,200 samples. For force learning on the MD17 dataset, our optimized model similarly displays state-of-the-art accuracy with a regressor based on Gaussian process regression. When the revised FCHL19 representation is combined with the operator quantum machine learning regressor, forces and energies can be predicted in only a few milliseconds per atom. The model presented herein is fast and lightweight enough for use in general chemistry problems as well as molecular dynamics simulations.

We consider the task of predicting Hamiltonian matrices to accelerate electronic structure calculations, which plays an important role in physics, chemistry, and materials science. Motivated by the inherent relationship between the off-diagonal blocks of the Hamiltonian matrix and the SO(2) local frame, we propose a novel and efficient network, called QHNetV2, that achieves global SO(3) equivariance without the costly SO(3) Clebsch-Gordan tensor products. This is achieved by introducing a set of new efficient and powerful SO(2)-equivariant operations and performing all off-diagonal feature updates and message passing within SO(2) local frames, thereby eliminating the need of SO(3) tensor products. Moreover, a continuous SO(2) tensor product is performed within the SO(2) local frame at each node to fuse node features, mimicking the symmetric contraction operation. Extensive experiments on the large QH9 and MD17 datasets demonstrate that our model achieves superior performance across a wide range of molecular structures and trajectories, highlighting its strong generalization capability. The proposed SO(2) operations on SO(2) local frames offer a promising direction for scalable and symmetry-aware learning of electronic structures. Our code will be released as part of the AIRS library https://github.com/divelab/AIRS.

Hamiltonian matrix prediction is pivotal in computational chemistry, serving as the foundation for determining a wide range of molecular properties. While SE(3) equivariant graph neural networks have achieved remarkable success in this domain, their substantial computational cost--driven by high-order tensor product (TP) operations--restricts their scalability to large molecular systems with extensive basis sets. To address this challenge, we introduce SPHNet, an efficient and scalable equivariant network, that incorporates adaptive SParsity into Hamiltonian prediction. SPHNet employs two innovative sparse gates to selectively constrain non-critical interaction combinations, significantly reducing tensor product computations while maintaining accuracy. To optimize the sparse representation, we develop a Three-phase Sparsity Scheduler, ensuring stable convergence and achieving high performance at sparsity rates of up to 70%. Extensive evaluations on QH9 and PubchemQH datasets demonstrate that SPHNet achieves state-of-the-art accuracy while providing up to a 7x speedup over existing models. Beyond Hamiltonian prediction, the proposed sparsification techniques also hold significant potential for improving the efficiency and scalability of other SE(3) equivariant networks, further broadening their applicability and impact. Our code can be found at https://github.com/microsoft/SPHNet.

The large and chemically diverse GMTKN55 benchmark was used as a training set for parametrizing composite wave function thermochemistry protocols akin to G4(MP2)XK theory (Chan et al, JCTC 2019, 15, 4478-4484). Even after reparametrization, the GMTKN55 WTMAD2 (weighted mean absolute deviation, type 2) for G4(MP2)-XK is actually inferior to that of the best rung-4 DFT functional, wB97M-V. By increasing the basis set for the MP2 part to def2-QZVPPD, we were able to substantially improve performance at modest cost (if an RI-MP2 approximation is made), with WTMAD2 for this G4(MP2)-XK-D method now comparable to the better rung-5 functionals (albeit at greater cost). A three-tier approach with a scaled MP3/def2-TZVPP intermediate step, however, leads to a G4(MP3)-D method that is markedly superior to even the best double hybrids wB97M(2) and revDSD-PBEP86-D4. Evaluating the CCSD(T) component with a triple-zeta, rather than split-valence, basis set yields only a modest further improvement that is incommensurate with the drastic increase in computational cost. G4(MP3)-D and G4(MP2)- XK-D have about 40% better WTMAD2, at similar or lower computational cost, than their counterparts G4 and G4(MP2), respectively: detailed comparison reveals that the difference lies in larger molecules due to basis set incompleteness error. An E2/ {T,Q} extrapolation and a CCSD(T)/def2-TZVP step provided the G4-T method of high accuracy and with just three fitted parameters. Using KS orbitals in MP2 leads to the G4(MP3|KS)-D method, which entirely eliminates the CCSD(T) step and has no steps costlier than scaled MP3; this shows a path forward to further improvements in double-hybrid density functional methods. G4-T-DLPNO, a variant in which post-MP2 corrections are evaluated at the DLPNO- CCSD(T) level, achieves nearly the accuracy of G4-T but is applicable to much larger systems.

The task of locating first order saddle points on high-dimensional surfaces describing the variation of energy as a function of atomic coordinates is an essential step for identifying the mechanism and estimating the rate of thermally activated events within the harmonic approximation of transition state theory. When combined directly with electronic structure calculations, the number of energy and atomic force evaluations needed for convergence is a primary issue. Here, we describe an efficient implementation of Gaussian process regression (GPR) acceleration of the minimum mode following method where a dimer is used to estimate the lowest eigenmode of the Hessian. A surrogate energy surface is constructed and updated after each electronic structure calculation. The method is applied to a test set of 500 molecular reactions previously generated by Hermez and coworkers [J. Chem. Theory Comput. 18, 6974 (2022)]. An order of magnitude reduction in the number of electronic structure calculations needed to reach the saddle point configurations is obtained by using the GPR compared to the dimer method. Despite the wide range in stiffness of the molecular degrees of freedom, the calculations are carried out using Cartesian coordinates and are found to require similar number of electronic structure calculations as an elaborate internal coordinate method implemented in the Sella software package. The present implementation of the GPR surrogate model in C++ is efficient enough for the wall time of the saddle point searches to be reduced in 3 out of 4 cases even though the calculations are carried out at a low Hartree-Fock level.

Fermi operator expansion (FOE) methods are powerful alternatives to diagonalization type methods for solving Kohn-Sham density functional theory (KSDFT). One example is the pole expansion and selected inversion (PEXSI) method, which approximates the Fermi operator by rational matrix functions and reduces the computational complexity to at most quadratic scaling for solving KSDFT. Unlike diagonalization type methods, the chemical potential often cannot be directly read off from the result of a single step of evaluation of the Fermi operator. Hence multiple evaluations are needed to be sequentially performed to compute the chemical potential to ensure the correct number of electrons within a given tolerance. This hinders the performance of FOE methods in practice. In this paper we develop an efficient and robust strategy to determine the chemical potential in the context of the PEXSI method. The main idea of the new method is not to find the exact chemical potential at each self-consistent-field (SCF) iteration iteration, but to dynamically and rigorously update the upper and lower bounds for the true chemical potential, so that the chemical potential reaches its convergence along the SCF iteration. Instead of evaluating the Fermi operator for multiple times sequentially, our method uses a two-level strategy that evaluates the Fermi operators in parallel. In the regime of full parallelization, the wall clock time of each SCF iteration is always close to the time for one single evaluation of the Fermi operator, even when the initial guess is far away from the converged solution. We demonstrate the effectiveness of the new method using examples with metallic and insulating characters, as well as results from ab initio molecular dynamics.

We combine a regularized variant of the strongly constrained and appropriately normed semilocal density functional [J. Sun, A. Ruzsinszky, and J. P. Perdew, Phys. Rev. Lett. 115, 036402 (2015)] with the latest generation semi-classical London dispersion correction. The resulting density functional approximation r2SCAN-D4 has the speed of generalized gradient approximations while approaching the accuracy of hybrid functionals for general chemical applications. We demonstrate its numerical robustness in real-life settings and benchmark molecular geometries, general main group and organo-metallic thermochemistry, as well as non-covalent interactions in supramolecular complexes and molecular crystals. Main group and transition metal bond lengths have errors of just 0.8%, which is competitive with hybrid functionals for main group molecules and outperforms them for transition metal complexes. The weighted mean absolute deviation (WTMAD2) on the large GMTKN55 database of chemical properties is exceptionally small at 7.5 kcal/mol. This also holds for metal organic reactions with an MAD of 3.3 kcal/mol. The versatile applicability to organic and metal-organic systems transfers to condensed systems, where lattice energies of molecular crystals are within chemical accuracy (errors <1 kcal/mol).

Accurate thermochemical data with sub-chemical accuracy (i.e., within pm1 kcal mol^{-1} from sufficiently accurate experimental or theoretical reference data) is essential for the development and improvement of computational chemistry methods. Challenging thermochemical properties such as heats of formation and total atomization energies (TAEs) are of particular interest because they rigorously test the ability of computational chemistry methods to accurately describe complex chemical transformations involving multiple bond rearrangements. Yet, existing thermochemical datasets that confidently reach this level of accuracy are limited in either size or scope. Datasets with highly accurate reference values include a small number of data points, and larger datasets provide less accurate data or only cover a narrow portion of the chemical space. The existing datasets are therefore insufficient for developing data-driven methods with predictive accuracy over a large chemical space. The Microsoft Research Accurate Chemistry Collection (MSR-ACC) will address this challenge. Here, it offers the MSR-ACC/TAE25 dataset of 76,879 total atomization energies obtained at the CCSD(T)/CBS level via the W1-F12 thermochemical protocol. The dataset is constructed to exhaustively cover chemical space for all elements up to argon by enumerating and sampling chemical graphs, thus avoiding bias towards any particular subspace of the chemical space (such as drug-like, organic, or experimentally observed molecules). With this first dataset in MSR-ACC, we enable data-driven approaches for developing predictive computational chemistry methods with unprecedented accuracy and scope.

Machine learning (ML) models hold the promise of transforming atomic simulations by delivering quantum chemical accuracy at a fraction of the computational cost. Realization of this potential would enable high-throughout, high-accuracy molecular screening campaigns to explore vast regions of chemical space and facilitate ab initio simulations at sizes and time scales that were previously inaccessible. However, a fundamental challenge to creating ML models that perform well across molecular chemistry is the lack of comprehensive data for training. Despite substantial efforts in data generation, no large-scale molecular dataset exists that combines broad chemical diversity with a high level of accuracy. To address this gap, Meta FAIR introduces Open Molecules 2025 (OMol25), a large-scale dataset composed of more than 100 million density functional theory (DFT) calculations at the omegaB97M-V/def2-TZVPD level of theory, representing billions of CPU core-hours of compute. OMol25 uniquely blends elemental, chemical, and structural diversity including: 83 elements, a wide-range of intra- and intermolecular interactions, explicit solvation, variable charge/spin, conformers, and reactive structures. There are ~83M unique molecular systems in OMol25 covering small molecules, biomolecules, metal complexes, and electrolytes, including structures obtained from existing datasets. OMol25 also greatly expands on the size of systems typically included in DFT datasets, with systems of up to 350 atoms. In addition to the public release of the data, we provide baseline models and a comprehensive set of model evaluations to encourage community engagement in developing the next-generation ML models for molecular chemistry.

Generative models have advanced significantly in sampling material systems with continuous variables, such as atomistic structures. However, their application to discrete variables, like atom types or spin states, remains underexplored. In this work, we introduce a Boltzmann generator built on discrete flow matching, specifically tailored for systems with discrete phase-space coordinates (e.g., the Ising model or crystalline compounds). This approach enables a single model to sample free energy surfaces over a wide temperature range with minimal training overhead. In addition, the model generation is scalable to larger lattice sizes than those in the training set. We demonstrate the effectiveness of our approach on the 2D Ising model, showing efficient and reliable free energy sampling. This framework provides a scalable and computationally efficient solution for discrete coordinate systems and can be extended to sample the alchemical degrees of freedom in crystalline compounds.

Variational optimization of neural-network representations of quantum states has been successfully applied to solve interacting fermionic problems. Despite rapid developments, significant scalability challenges arise when considering molecules of large scale, which correspond to non-locally interacting quantum spin Hamiltonians consisting of sums of thousands or even millions of Pauli operators. In this work, we introduce scalable parallelization strategies to improve neural-network-based variational quantum Monte Carlo calculations for ab-initio quantum chemistry applications. We establish GPU-supported local energy parallelism to compute the optimization objective for Hamiltonians of potentially complex molecules. Using autoregressive sampling techniques, we demonstrate systematic improvement in wall-clock timings required to achieve CCSD baseline target energies. The performance is further enhanced by accommodating the structure of resultant spin Hamiltonians into the autoregressive sampling ordering. The algorithm achieves promising performance in comparison with the classical approximate methods and exhibits both running time and scalability advantages over existing neural-network based methods.

The Schr\"odinger Bridge (SB) is a powerful framework for solving generative modeling tasks such as unpaired domain translation. Most SB-related research focuses on continuous data space R^{D} and leaves open theoretical and algorithmic questions about applying SB methods to discrete data, e.g, on finite spaces S^{D}. Notable examples of such sets S are codebooks of vector-quantized (VQ) representations of modern autoencoders, tokens in texts, categories of atoms in molecules, etc. In this paper, we provide a theoretical and algorithmic foundation for solving SB in discrete spaces using the recently introduced Iterative Markovian Fitting (IMF) procedure. Specifically, we theoretically justify the convergence of discrete-time IMF (D-IMF) to SB in discrete spaces. This enables us to develop a practical computational algorithm for SB which we call Categorical Schr\"odinger Bridge Matching (CSBM). We show the performance of CSBM via a series of experiments with synthetic data and VQ representations of images.

Accurate potential energy surface (PES) descriptions are essential for atomistic simulations of materials. Universal machine learning interatomic potentials (UMLIPs)^{1-3} offer a computationally efficient alternative to density functional theory (DFT)^4 for PES modeling across the periodic table. However, their accuracy today is fundamentally constrained due to a reliance on DFT relaxation data.^{5,6} Here, we introduce MatPES, a foundational PES dataset comprising sim 400,000 structures carefully sampled from 281 million molecular dynamics snapshots that span 16 billion atomic environments. We demonstrate that UMLIPs trained on the modestly sized MatPES dataset can rival, or even outperform, prior models trained on much larger datasets across a broad range of equilibrium, near-equilibrium, and molecular dynamics property benchmarks. We also introduce the first high-fidelity PES dataset based on the revised regularized strongly constrained and appropriately normed (r^2SCAN) functional^7 with greatly improved descriptions of interatomic bonding. The open source MatPES initiative emphasizes the importance of data quality over quantity in materials science and enables broad community-driven advancements toward more reliable, generalizable, and efficient UMLIPs for large-scale materials discovery and design.

Multireference density functional theory (MR-DFT) provides a pivotal microscopic framework for the description of the ground state properties, low-lying nuclear spectra and transition properties of atomic nuclei. Conventionally, practical implementations of MR-DFT rely on empirically chosen generator coordinates, which may omit relevant collective degrees of freedom and thus fail to capture sufficient collective correlations. Here we introduce the stochastic-basis multireference density functional theory (MR-SDFT). This is an extended scheme that augments the MR-DFT toolkit by (i) generating a diverse ensemble of mean-field reference configurations via a stochastic external field and (ii) selecting a compact subspace with Projection-Selection method. The chosen reference configurations are then linearly superposed within the MR-DFT framework to yield spectroscopic observables. Applying this framework to \nuclide[20]{Ne}, \nuclide[24]{Mg} and \nuclide[28]{Si} with the covariant density functional theory (CDFT), it is demonstrated that the MR-SCDFT leads to lower ground-state energies, smaller point-proton rms radius, and a softer ground-state band compared to the conventional MR-CDFT.

Machine-learning (ML) force fields enable large-scale simulations with near-first-principles accuracy at substantially reduced computational cost. Recent work has extended ML force-field approaches to adiabatic dynamical simulations of condensed-matter lattice models with coupled electronic and structural or magnetic degrees of freedom. However, most existing formulations rely on hand-crafted, symmetry-aware descriptors, whose construction is often system-specific and can hinder generality and transferability across different lattice Hamiltonians. Here we introduce a symmetry-preserving framework based on equivariant neural networks (ENNs) that provides a general, data-driven mapping from local configurations of dynamical variables to the associated on-site forces in a lattice Hamiltonian. In contrast to ENN architectures developed for molecular systems -- where continuous Euclidean symmetries dominate -- our approach aims to embed the discrete point-group and internal symmetries intrinsic to lattice models directly into the neural-network representation of the force field. As a proof of principle, we construct an ENN-based force-field model for the adiabatic dynamics of the Holstein Hamiltonian on a square lattice, a canonical system for electron-lattice physics. The resulting ML-enabled large-scale dynamical simulations faithfully capture mesoscale evolution of the symmetry-breaking phase, illustrating the utility of lattice-equivariant architectures for linking microscopic electronic processes to emergent dynamical behavior in condensed-matter lattice systems.

The application of language models (LMs) to molecular structure generation using line notations such as SMILES and SELFIES has been well-established in the field of cheminformatics. However, extending these models to generate 3D molecular structures presents significant challenges. Two primary obstacles emerge: (1) the difficulty in designing a 3D line notation that ensures SE(3)-invariant atomic coordinates, and (2) the non-trivial task of tokenizing continuous coordinates for use in LMs, which inherently require discrete inputs. To address these challenges, we propose Mol-StrucTok, a novel method for tokenizing 3D molecular structures. Our approach comprises two key innovations: (1) We design a line notation for 3D molecules by extracting local atomic coordinates in a spherical coordinate system. This notation builds upon existing 2D line notations and remains agnostic to their specific forms, ensuring compatibility with various molecular representation schemes. (2) We employ a Vector Quantized Variational Autoencoder (VQ-VAE) to tokenize these coordinates, treating them as generation descriptors. To further enhance the representation, we incorporate neighborhood bond lengths and bond angles as understanding descriptors. Leveraging this tokenization framework, we train a GPT-2 style model for 3D molecular generation tasks. Results demonstrate strong performance with significantly faster generation speeds and competitive chemical stability compared to previous methods. Further, by integrating our learned discrete representations into Graphormer model for property prediction on QM9 dataset, Mol-StrucTok reveals consistent improvements across various molecular properties, underscoring the versatility and robustness of our approach.

The development of reliable and extensible molecular mechanics (MM) force fields -- fast, empirical models characterizing the potential energy surface of molecular systems -- is indispensable for biomolecular simulation and computer-aided drug design. Here, we introduce a generalized and extensible machine-learned MM force field, espaloma-0.3, and an end-to-end differentiable framework using graph neural networks to overcome the limitations of traditional rule-based methods. Trained in a single GPU-day to fit a large and diverse quantum chemical dataset of over 1.1M energy and force calculations, espaloma-0.3 reproduces quantum chemical energetic properties of chemical domains highly relevant to drug discovery, including small molecules, peptides, and nucleic acids. Moreover, this force field maintains the quantum chemical energy-minimized geometries of small molecules and preserves the condensed phase properties of peptides, self-consistently parametrizing proteins and ligands to produce stable simulations leading to highly accurate predictions of binding free energies. This methodology demonstrates significant promise as a path forward for systematically building more accurate force fields that are easily extensible to new chemical domains of interest.

Generative machine learning models can potentially provide direct access to novel and relevant portions of the full chemical space, overcoming the cost of systematic sampling. However, the training of these models generally requires a large amount of data, often precluding the use of expensive high-level ab initio simulations for this task. The generation of coordination compounds of Dy with large magnetic anisotropy represents a topical example, where multireference simulations of large molecules are necessary to perform reliable predictions. Here, we show that a semi-supervised chemically-inspired training-by-proxy of generative variational autoencoders can reduce the cost associated with building a training set from multireference simulations by two orders of magnitude. We illustrate the power of this approach by generating 100s of new organic ligands for Dy(III) pentagonal bipyramidal complexes exhibiting record values of magnetic anisotropy, while starting from datasets as small as 1k multireference calculations. This work thus paves the way to the computational generation of molecules as complex coordination compounds with target electronic and magnetic properties.

High-performance computing (HPC) is increasingly important for scalable quantum chemistry workflows that couple classical generative models, quantum circuit simulation, and selected configuration interaction postprocessing. We present the generative quantum-inspired Kolmogorov-Arnold eigensolver (GQKAE), a parameter-efficient extension of the generative quantum eigensolver (GQE) for quantum chemistry. GQKAE replaces the parameter-heavy feed-forward network components in GPT-style generative eigensolvers with hybrid quantum-inspired Kolmogorov-Arnold network modules, forming a compact HQKANsformer backbone. The method preserves autoregressive operator selection and the quantum-selected configuration interaction evaluation pipeline, while using single-qubit DatA Re-Uploading ActivatioN modules to provide expressive nonlinear mappings. Numerical benchmarks on H4, N2, LiH, C2H6, H2O, and the H2O dimer show that GQKAE achieves chemical accuracy comparable to the GPT-based GQE architecture, while reducing trainable parameters and memory by approximately 66% and improving wall-time performance. For strongly correlated systems such as N2 and LiH, GQKAE also improves convergence behavior and final energy errors. These results indicate that quantum-inspired Kolmogorov-Arnold networks can reduce classical-side overhead while preserving circuit-generation quality, offering a scalable route for HPC-quantum co-design on near-term quantum platforms.

We present THEMol (Torsion, Hessian, Energy of Molecules), a massive open-source collection of quantum mechanical properties tailored for closed-shell organic molecules, with up to 50 heavy atoms. THEMol includes a Hessian subset with more than 3 million relaxed geometries with Hessian matrices, a TorsionScan subset with nearly 100 million constrained relaxed geometries with energies and forces, and relaxation-trajectory subsets (HessianRelax and TorsionScanRelax) that together comprise about 3 billion DFT calculations. The chemical space sampling is comprehensive, spanning twelve essential elements and diverse molecular architectures relevant to drug discovery, electrolytes, ionic liquids, and beyond. The dataset also features exhaustive conformational sampling through the TorsionScan and TorsionScanRelax subsets, including comprehensive in-ring and non-ring torsional scans. Furthermore, it contains an extensive library of Hessian matrices, computed at relaxed geometries, to capture critical second-derivative information of the potential energy landscape. Additionally, we supply electron density-derived atomic multipoles computed via the Minimal Basis Iterative Stockholder partition scheme. Organized into five distinct subsets (Hessian, TorsionScan, HessianRelax, TorsionScanRelax, and MBIS), the data encompasses optimized geometries, relaxation trajectories, and derived molecular properties. We anticipate that this massive and diverse dataset will significantly empower the development of highly accurate and transferable molecular potentials.

Accurate prediction of atomistic, thermodynamic, and kinetic properties from molecular structures underpins materials innovation. Existing computational and experimental approaches lack the scalability required to efficiently navigate chemical space. Scientific foundation models trained on large unlabeled datasets offer a path toward exploring chemical space across diverse application domains. Here we develop MIST, a family of molecular foundation models with up to an order of magnitude more parameters and data than prior works. Trained using a novel tokenization scheme that comprehensively captures nuclear, electronic, and geometric information, MIST learns from a diverse range of molecules. MIST models have been fine-tuned to predict more than 400 structure -- property relationships and match or exceed state-of-the-art performance across benchmarks spanning physiology, electrochemistry, and quantum chemistry. We demonstrate the ability of these models to solve real-world problems across chemical space, including multiobjective electrolyte solvent screening, olfactory perception mapping, isotope half-life prediction, stereochemical reasoning for chiral organometallic compounds, and binary and multi-component mixture property prediction. Probing MIST models using mechanistic interpretability methods reveals identifiable patterns and trends not explicitly present in the training data, suggesting that the models learn generalizable scientific concepts. We formulate hyperparameter-penalized Bayesian neural scaling laws and use them to reduce the computational cost of model development by an order of magnitude. The methods and findings presented here represent a significant step toward accelerating materials discovery, design, and optimization using foundation models and provide valuable guidance for training compute-optimal scientific foundation models.

The overwhelming majority of molecules remains unexplored. This is mostly due to the sheer number of them, which prohibits any enumeration of chemical space, the set of all such molecules. In practice, only subsets of chemical space are considered, but those subsets exhibit substantial bias, prohibiting data-driven characterization of chemical space itself. In this work, we provide a method produce unbiased representative random samples of chemical space without enumeration of constituent molecules and to estimate the number of molecules in any custom chemical space. The approach is applicable to molecules which can be represented as graph and runs efficiently even for molecules of 30 atoms. We use it to estimate the representativeness of current databases with respect to their underlying chemical space and to establish a necessary criterion for a lower bound of database sizes to be representative of an underlying chemical space.

Networks of atom-centered coordination octahedra commonly occur in inorganic and hybrid solid-state materials. Characterizing their spatial arrangements and characteristics is crucial for relating structures to properties for many materials families. The traditional method using case-by-case inspection becomes prohibitive for discovering trends and similarities in large datasets. Here, we operationalize chemical intuition to automate the geometric parsing, quantification, and classification of coordination octahedral networks. We find axis-resolved tilting trends in ABO_{3} perovskite polymorphs, which assist in detecting oxidation state changes. Moreover, we develop a scale-invariant encoding scheme to represent these networks, which, combined with human-assisted unsupervised machine learning, allows us to taxonomize the inorganic framework polytypes in hybrid iodoplumbates (A_xPb_yI_z). Consequently, we uncover a violation of Pauling's third rule and the design principles underpinning their topological diversity. Our results offer a glimpse into the vast design space of atomic octahedral networks and inform high-throughput, targeted screening of specific structure types.

Density functional theory (DFT), the most widely adopted method in modern computational chemistry, fails to describe accurately the electronic structure of strongly correlated systems. Here we show that DFT can be formally and practically transformed into a one-electron reduced-density-matrix (1-RDM) functional theory, which can address the limitations of DFT while retaining favorable computational scaling compared to wavefunction-based approaches. In addition to relaxing the idempotency restriction on the 1-RDM in the kinetic energy term, we add a quadratic 1-RDM-based term to DFT's density-based exchange-correlation functional. Our approach, which we implement by quadratic semidefinite programming at DFT's computational scaling of O(r^{3}), yields substantial improvements over traditional DFT in the description of static correlation in chemical structures and processes such as singlet biradicals and bond dissociations.

Creating a single unified interatomic potential capable of attaining ab initio accuracy across all chemistry remains a long-standing challenge in computational chemistry and materials science. This work introduces a training protocol for foundation machine-learning interatomic potentials (MLIPs) that bridge molecular, surface, and materials chemistry through cross-domain learning. First, we introduce enhancements to the MACE architecture that improve its performance on chemically diverse databases by increasing weight sharing across chemical elements and introducing non-linear factors into the tensor decomposition of the product basis. Second, we develop a multi-head replay post-training methodology that enables efficient knowledge transfer across diverse chemical domains. By fine-tuning on datasets at different levels of electronic structure theory, including inorganic crystals, molecular systems, surface chemistry, and reactive organic chemistry, we demonstrate that a single unified model achieves state-of-the-art performance across several chemical domains. Comprehensive benchmarking reveals superior cross-domain transferability compared with existing specialised and multi-task models, with notable improvements in molecular and surface properties while maintaining state-of-the-art performance in materials-property prediction.

Organic Solar Cells are a promising technology for solving the clean energy crisis in the world. However, generating candidate chemical compounds for solar cells is a time-consuming process requiring thousands of hours of laboratory analysis. For a solar cell, the most important property is the power conversion efficiency which is dependent on the highest occupied molecular orbitals (HOMO) values of the donor molecules. Recently, machine learning techniques have proved to be very useful in building predictive models for HOMO values of donor structures of Organic Photovoltaic Cells (OPVs). Since experimental datasets are limited in size, current machine learning models are trained on data derived from calculations based on density functional theory (DFT). Molecular line notations such as SMILES or InChI are popular input representations for describing the molecular structure of donor molecules. The two types of line representations encode different information, such as SMILES defines the bond types while InChi defines protonation. In this work, we present an ensemble deep neural network architecture, called SINet, which harnesses both the SMILES and InChI molecular representations to predict HOMO values and leverage the potential of transfer learning from a sizeable DFT-computed dataset- Harvard CEP to build more robust predictive models for relatively smaller HOPV datasets. Harvard CEP dataset contains molecular structures and properties for 2.3 million candidate donor structures for OPV while HOPV contains DFT-computed and experimental values of 350 and 243 molecules respectively. Our results demonstrate significant performance improvement from the use of transfer learning and leveraging both molecular representations.

Foundation machine-learned interatomic potentials (MLIPs) are trained on large quantum-mechanical datasets and generalise across broad regions of chemical and configurational space. Beyond their usual role in accelerating sampling-based simulations, their internal representations encode chemically rich local atomic environments. Here, we introduce Rem3Di, a representation-learning framework that repurposes latent features from atomistic foundation models as transferable molecular descriptors for property prediction and virtual screening. Rem3Di combines a potential's per-atom features into a single fixed-length descriptor of the whole molecule that varies smoothly with three-dimensional structure and is invariant to the ordering of the atoms. The descriptor can be used directly or fine-tuned for specific prediction tasks. To capture molecular handedness, Rem3Di constructs pseudoscalar features, which are unchanged by rotation but reverse sign under mirror reflection. This lets the descriptor distinguish enantiomers, which can differ in activity and toxicity. The transformer is pretrained on large molecular datasets by reconstructing corrupted atom features, so no experimental labels are required. Across public drug-property benchmarks, Rem3Di matches or exceeds published baselines without relying on classical 2D fingerprints. Additionally, the same descriptor yields chemically meaningful differentiation of transition-metal complexes without predefined bonding rules or handcrafted representations. Rem3Di therefore provides a route from simulation-trained atomistic representations to transferable, chirality-aware molecular representations for chemical machine learning.

The ability to quickly and accurately compute properties from atomic simulations is critical for advancing a large number of applications in chemistry and materials science including drug discovery, energy storage, and semiconductor manufacturing. To address this need, Meta FAIR presents a family of Universal Models for Atoms (UMA), designed to push the frontier of speed, accuracy, and generalization. UMA models are trained on half a billion unique 3D atomic structures (the largest training runs to date) by compiling data across multiple chemical domains, e.g. molecules, materials, and catalysts. We develop empirical scaling laws to help understand how to increase model capacity alongside dataset size to achieve the best accuracy. The UMA small and medium models utilize a novel architectural design we refer to as mixture of linear experts that enables increasing model capacity without sacrificing speed. For example, UMA-medium has 1.4B parameters but only ~50M active parameters per atomic structure. We evaluate UMA models on a diverse set of applications across multiple domains and find that, remarkably, a single model without any fine-tuning can perform similarly or better than specialized models. We are releasing the UMA code, weights, and associated data to accelerate computational workflows and enable the community to continue to build increasingly capable AI models.

The discovery of next-generation photoinitiators for two-photon polymerization (TPP) is hindered by the absence of large, open datasets containing the quantum-chemical and photophysical properties required to model photodissociation and excited-state behavior. Existing molecular datasets typically provide only basic physicochemical descriptors and therefore cannot support data-driven screening or AI-assisted design of photoinitiators. To address this gap, we introduce QuantumChem-200K, a large-scale dataset of over 200,000 organic molecules annotated with eleven quantum-chemical properties, including two-photon absorption (TPA) cross sections, TPA spectral ranges, singlet-triplet intersystem crossing (ISC) energies, toxicity and synthetic accessibility scores, hydrophilicity, solubility, boiling point, molecular weight, and aromaticity. These values are computed using a hybrid workflow that integrates density function theory (DFT), semi-empirical excited-state methods, atomistic quantum solvers, and neural-network predictors. Using QuantumChem-200K, we fine tune the open-source Qwen2.5-32B large language model to create a chemistry AI assistant capable of forward property prediction from SMILES. Benchmarking on 3000 unseen molecules from VQM24 and ZINC20 demonstrates that domain-specific fine-tuning significantly improves accuracy over GPT-4o, Llama-3.1-70B, and the base Qwen2.5-32B model, particularly for TPA and ISC predictions central to photoinitiator design. QuantumChem-200K and the corresponding AI assistant together provide the first scalable platform for high-throughput, LLM-driven photoinitiator screening and accelerated discovery of photosensitive materials.

We present a vector-based method to balance chemical reactions. The algorithm builds candidates in a deterministic way, removes duplicates, and always prints coefficients in the lowest whole-number form. For redox cases, electrons and protons/hydroxide are treated explicitly, so both mass and charge are balanced. We also outline the basic principles of the vector formulation of stoichiometry, interpreting reactions as integer vectors in composition space, this geometric view supports compact visualizations of reagent-product interactions and helps surface distinct reaction families. The method enumerates valid balances for arbitrary user-specified species lists without special-case balancing rules or symbolic tricks, and it provides a clean foundation for developing new algorithmic variants (e.g., alternative objectives or constraints). On representative examples (neutralization, double displacement, decomposition, classical redox, small multicomponent sets) and a negative control, the method produced correct integer balances. When multiple balances exist, we report a canonical one - minimizing the total coefficient sum with a simple tie-breaker - without claiming global optimality beyond the solutions the search enumerates. The procedure applies per reaction and extends to reaction networks via consistent per-reaction application. We do not report runtimes, broader benchmarking and code/data release are planned.

Accurate prediction of bond dissociation energies (BDEs) underpins mechanistic insight and the rational design of molecules and materials. We present a systematic, reproducible benchmark comparing quantum and classical machine learning models for BDE prediction using a chemically curated feature set encompassing atomic properties (atomic numbers, hybridization), bond characteristics (bond order, type), and local environmental descriptors. Our quantum framework, implemented in Qiskit Aer on six qubits, employs ZZFeatureMap encodings with variational ansatz (RealAmplitudes) across multiple architectures Variational Quantum Regressors (VQR), Quantum Support Vector Regressors (QSVR), Quantum Neural Networks (QNN), Quantum Convolutional Neural Networks (QCNN), and Quantum Random Forests (QRF). These are rigorously benchmarked against strong classical baselines, including Support Vector Regression (SVR), Random Forests (RF), and Multi-Layer Perceptrons (MLP). Comprehensive evaluation spanning absolute and relative error metrics, threshold accuracies, and error distributions shows that top-performing quantum models (QCNN, QRF) match the predictive accuracy and robustness of classical ensembles and deep networks, particularly within the chemically prevalent mid-range BDE regime. These findings establish a transparent baseline for quantum-enhanced molecular property prediction and outline a practical foundation for advancing quantum computational chemistry toward near chemical accuracy.

The prediction of phase diagrams in the search for new phases is a complex and computationally intensive task. Density functional theory provides, in many situations, the desired accuracy, but its throughput becomes prohibitively limited as the number of species involved grows, even when used with local and semi-local functionals. Here, we explore the possibility of integrating machine-learning models in the workflow for the construction of ternary convex hull diagrams. In particular, we train a set of spectral neighbour-analysis potentials (SNAPs) over readily available binary phases and we establish whether this is good enough to predict the energies of novel ternaries. Such a strategy does not require any new calculations specific for the construction of the model, but just avails of data stored in binary-phase-diagram repositories. We find that a so-constructed SNAP is capable of accurate total-energy estimates for ternary phases close to the equilibrium geometry but, in general, is not able to perform atomic relaxation. This is because during a typical relaxation path a given phase traverses regions in the parameter space poorly represented by the training set. Different metrics are then investigated to assess how an unknown structure is well described by a given SNAP model, and we find that the standard deviation of an ensemble of SNAPs provides a fast and non-specie-specific metric.

We propose a simple auto-encoder framework for molecule generation. The molecular graph is first encoded into a continuous latent representation z, which is then decoded back to a molecule. The encoding process is easy, but the decoding process remains challenging. In this work, we introduce a simple two-step decoding process. In a first step, a fully connected neural network uses the latent vector z to produce a molecular formula, for example CO_2 (one carbon and two oxygen atoms). In a second step, a graph convolutional neural network uses the same latent vector z to place bonds between the atoms that were produced in the first step (for example a double bond will be placed between the carbon and each of the oxygens). This two-step process, in which a bag of atoms is first generated, and then assembled, provides a simple framework that allows us to develop an efficient molecule auto-encoder. Numerical experiments on basic tasks such as novelty, uniqueness, validity and optimized chemical property for the 250k ZINC molecules demonstrate the performances of the proposed system. Particularly, we achieve the highest reconstruction rate of 90.5\%, improving the previous rate of 76.7\%. We also report the best property improvement results when optimization is constrained by the molecular distance between the original and generated molecules.

This paper challenges the recent paradigm in atomic property prediction that links progress to growing dataset sizes and computational resources. We show that pretraining on a carefully selected, task-relevant dataset can match or even surpass large-scale pretraining, while using as little as 1/24th of the computational cost. We introduce the Chemical Similarity Index (CSI), a novel metric inspired by computer vision's Fr\'echet Inception Distance, for molecular graphs which quantifies the alignment between upstream pretraining datasets and downstream tasks. By selecting the most relevant dataset with minimal CSI distance, we show that models pretrained on a smaller, focused dataset consistently outperform those pretrained on massive, mixed datasets such as JMP, even when those larger datasets include the relevant dataset. Counterintuitively, we also find that indiscriminately adding more data can degrade model performance when the additional data poorly aligns with the task at hand. Our findings highlight that quality often outperforms quantity in pretraining for atomic property prediction.

Accurately predicting experimentally realizable 3D molecular crystal structures from their 2D chemical graphs is a long-standing open challenge in computational chemistry called crystal structure prediction (CSP). Efficiently solving this problem has implications ranging from pharmaceuticals to organic semiconductors, as crystal packing directly governs the physical and chemical properties of organic solids. In this paper, we introduce OXtal, a large-scale 100M parameter all-atom diffusion model that directly learns the conditional joint distribution over intramolecular conformations and periodic packing. To efficiently scale OXtal, we abandon explicit equivariant architectures imposing inductive bias arising from crystal symmetries in favor of data augmentation strategies. We further propose a novel crystallization-inspired lattice-free training scheme, Stoichiometric Stochastic Shell Sampling (S^4), that efficiently captures long-range interactions while sidestepping explicit lattice parametrization -- thus enabling more scalable architectural choices at all-atom resolution. By leveraging a large dataset of 600K experimentally validated crystal structures (including rigid and flexible molecules, co-crystals, and solvates), OXtal achieves orders-of-magnitude improvements over prior ab initio machine learning CSP methods, while remaining orders of magnitude cheaper than traditional quantum-chemical approaches. Specifically, OXtal recovers experimental structures with conformer RMSD_1<0.5 Å and attains over 80\% packing similarity rate, demonstrating its ability to model both thermodynamic and kinetic regularities of molecular crystallization.

We explore the integration of Kolmogorov Networks (KANs) into molecular dynamics (MD) simulations to improve interatomic potentials. We propose that widely used potentials, such as the Lennard-Jones (LJ) potential, the embedded atom model (EAM), and artificial neural network (ANN) potentials, can be interpreted within the KAN framework. Specifically, we demonstrate that the descriptors for ANN potentials, typically constructed using polynomials, can be redefined using KAN's non-linear functions. By employing linear or cubic spline interpolations for these KAN functions, we show that the computational cost of evaluating ANN potentials and their derivatives is reduced.

In the search for novel intermetallic ternary alloys, much of the effort goes into performing a large number of ab-initio calculations covering a wide range of compositions and structures. These are essential to build a reliable convex hull diagram. While density functional theory (DFT) provides accurate predictions for many systems, its computational overheads set a throughput limit on the number of hypothetical phases that can be probed. Here, we demonstrate how an ensemble of machine-learning spectral neighbor-analysis potentials (SNAPs) can be integrated into a workflow for the construction of accurate ternary convex hull diagrams, highlighting regions fertile for materials discovery. Our workflow relies on using available binary-alloy data both to train the SNAP models and to create prototypes for ternary phases. From the prototype structures, all unique ternary decorations are created and used to form a pool of candidate compounds. The SNAPs are then used to pre-relax the structures and screen the most favourable prototypes, before using DFT to build the final phase diagram. As constructed, the proposed workflow relies on no extra first-principles data to train the machine-learning surrogate model and yields a DFT-level accurate convex hull. We demonstrate its efficacy by investigating the Cu-Ag-Au and Mo-Ta-W ternary systems.

The search for low-cost, durable, and effective catalysts is essential for green hydrogen production and carbon dioxide upcycling to help in the mitigation of climate change. Discovery of new catalysts is currently limited by the gap between what AI-accelerated computational models predict and what experimental studies produce. To make progress, large and diverse experimental datasets are needed that are reproducible and tested at industrially-relevant conditions. We address these needs by utilizing a comprehensive high-throughput characterization and experimental pipeline to create the Open Catalyst Experiments 2024 (OCX24) dataset. The dataset contains 572 samples synthesized using both wet and dry methods with X-ray fluorescence and X-ray diffraction characterization. We prepared 441 gas diffusion electrodes, including replicates, and evaluated them using zero-gap electrolysis for carbon dioxide reduction (CO_2RR) and hydrogen evolution reactions (HER) at current densities up to 300 mA/cm^2. To find correlations with experimental outcomes and to perform computational screens, DFT-verified adsorption energies for six adsorbates were calculated on sim20,000 inorganic materials requiring 685 million AI-accelerated relaxations. Remarkably from this large set of materials, a data driven Sabatier volcano independently identified Pt as being a top candidate for HER without having any experimental measurements on Pt or Pt-alloy samples. We anticipate the availability of experimental data generated specifically for AI training, such as OCX24, will significantly improve the utility of computational models in selecting materials for experimental screening.

Quantum computers can be used to address molecular structure, materials science and condensed matter physics problems, which currently stretch the limits of existing high-performance computing resources. Finding exact numerical solutions to these interacting fermion problems has exponential cost, while Monte Carlo methods are plagued by the fermionic sign problem. These limitations of classical computational methods have made even few-atom molecular structures problems of practical interest for medium-sized quantum computers. Yet, thus far experimental implementations have been restricted to molecules involving only Period I elements. Here, we demonstrate the experimental optimization of up to six-qubit Hamiltonian problems with over a hundred Pauli terms, determining the ground state energy for molecules of increasing size, up to BeH2. This is enabled by a hardware-efficient variational quantum eigensolver with trial states specifically tailored to the available interactions in our quantum processor, combined with a compact encoding of fermionic Hamiltonians and a robust stochastic optimization routine. We further demonstrate the flexibility of our approach by applying the technique to a problem of quantum magnetism. Across all studied problems, we find agreement between experiment and numerical simulations with a noisy model of the device. These results help elucidate the requirements for scaling the method to larger systems, and aim at bridging the gap between problems at the forefront of high-performance computing and their implementation on quantum hardware.

Universal machine learning force fields (UMLFFs) promise to revolutionize materials science by enabling rapid atomistic simulations across the periodic table. However, their evaluation has been limited to computational benchmarks that may not reflect real-world performance. Here, we present UniFFBench, a comprehensive framework for evaluating UMLFFs against experimental measurements of ~1,500 carefully curated mineral structures spanning diverse chemical environments, bonding types, structural complexity, and elastic properties. Our systematic evaluation of six state-of-the-art UMLFFs reveals a substantial reality gap: models achieving impressive performance on computational benchmarks often fail when confronted with experimental complexity. Even the best-performing models exhibit higher density prediction error than the threshold required for practical applications. Most strikingly, we observe disconnects between simulation stability and mechanical property accuracy, with prediction errors correlating with training data representation rather than the modeling method. These findings demonstrate that while current computational benchmarks provide valuable controlled comparisons, they may overestimate model reliability when extrapolated to experimentally complex chemical spaces. Altogether, UniFFBench establishes essential experimental validation standards and reveals systematic limitations that must be addressed to achieve truly universal force field capabilities.

Machine learning interatomic potentials (MLIPs) balance high accuracy and lower costs compared to density functional theory calculations, but their performance often depends on the size and diversity of training datasets. Large datasets improve model accuracy and generalization but are computationally expensive to produce and train on, while smaller datasets risk discarding rare but important atomic environments and compromising MLIP accuracy/reliability. Here, we develop an information-theoretical framework to quantify the efficiency of dataset compression methods and propose an algorithm that maximizes this efficiency. By framing atomistic dataset compression as an instance of the minimum set cover (MSC) problem over atom-centered environments, our method identifies the smallest subset of structures that contains as much information as possible from the original dataset while pruning redundant information. The approach is extensively demonstrated on the GAP-20 and TM23 datasets, and validated on 64 varied datasets from the ColabFit repository. Across all cases, MSC consistently retains outliers, preserves dataset diversity, and reproduces the long-tail distributions of forces even at high compression rates, outperforming other subsampling methods. Furthermore, MLIPs trained on MSC-compressed datasets exhibit reduced error for out-of-distribution data even in low-data regimes. We explain these results using an outlier analysis and show that such quantitative conclusions could not be achieved with conventional dimensionality reduction methods. The algorithm is implemented in the open-source QUESTS package and can be used for several tasks in atomistic modeling, from data subsampling, outlier detection, and training improved MLIPs at a lower cost.

We present a scheme to obtain an inexpensive and reliable estimate of the uncertainty associated with the predictions of a machine-learning model of atomic and molecular properties. The scheme is based on resampling, with multiple models being generated based on sub-sampling of the same training data. The accuracy of the uncertainty prediction can be benchmarked by maximum likelihood estimation, which can also be used to correct for correlations between resampled models, and to improve the performance of the uncertainty estimation by a cross-validation procedure. In the case of sparse Gaussian Process Regression models, this resampled estimator can be evaluated at negligible cost. We demonstrate the reliability of these estimates for the prediction of molecular energetics, and for the estimation of nuclear chemical shieldings in molecular crystals. Extension to estimate the uncertainty in energy differences, forces, or other correlated predictions is straightforward. This method can be easily applied to other machine learning schemes, and will be beneficial to make data-driven predictions more reliable, and to facilitate training-set optimization and active-learning strategies.

Accurate determination of transition states is central to an understanding of reaction kinetics. Double-endpoint methods where both initial and final states are specified, such as the climbing image nudged elastic band (CI-NEB), identify the minimum energy path between the two and thereby the saddle point on the energy surface that is relevant for the given transition, thus providing an estimate of the transition state within the harmonic approximation of transition state theory. Such calculations can, however, incur high computational costs and may suffer stagnation on exceptionally flat or rough energy surfaces. Conversely, methods that only require specification of an initial set of atomic coordinates, such as the minimum mode following (MMF) method, offer efficiency but can converge on saddle points that are not relevant for transition of interest. Here, we present an adaptive hybrid algorithm that integrates the CI-NEB with the MMF method so as to get faster convergence to the relevant saddle point. The method is benchmarked for the Baker-Chan (BC) saddle point test set using the PET-MAD machine-learned potential as well as 59 transitions of a heptamer island on Pt(111) from the OptBench benchmark set. A Bayesian analysis of the performance shows a reduction in energy and force calculations of 57% [95% CrI: -64%, -50%] relative to CI-NEB for the BC set, while a 31% mean reduction is found for the transitions of the heptamer island. These results establish this hybrid method as a highly effective tool for high-throughput automated chemical discovery of atomic rearrangements.

Organic crystal structure prediction (CSP) is a requirement for computational modelling of organic solids, but traditionally costs several CPU-years per molecule. Generative models such as OXtal dramatically reduce this cost by sampling stable organic crystal structures directly. However, OXtal forgoes explicit lattice parametrization in favour of modelling large crops of the bulk material with expensive triangle layers, which can incur a computational cost of minutes per molecule. In this paper, we reduce this to seconds with Clari, a large-scale flow matching model that generates redundancy-free unit cells and replaces triangle layers with pure pair-bias attention. Clari requires only atom types and bonds as input and does not need an RDKit-sanitizable input molecule, which expands its applicability to challenging chemistries such as fullerenes, metal complexes, and atom clusters. We further ablate key design choices such as auxiliary losses, timestep distributions, noise priors, and self-conditioning. On OXtal's test sets, we surpass OXtal's solve rate while obtaining a speedup of 15-30times. Because Clari also models explicit hydrogens, it supports inference-time scaling via direct energy ranking, without any decoration or relaxation step. When generating 150 crystals and selecting the top-30 by energy, we further improve solve rate while maintaining a speedup of 5-8times. We also introduce the CSD Teaching Subset as a new test split of diverse and complex molecules for future benchmarking. Our contributions enable CSP within seconds, making large-scale virtual screening of organic solids practical. Code is available at https://github.com/aspuru-guzik-group/clari.

The groundbreaking advance in materials and chemical research has been driven by the development of atomistic simulations. However, the broader applicability of the atomistic simulations remains restricted, as they inherently depend on energy models that are either inaccurate or computationally prohibitive. Machine learning interatomic potentials (MLIPs) have recently emerged as a promising class of energy models, but their deployment remains challenging due to the lack of systematic protocols for generating diverse training data. Here we automate the construction of training datasets to enable the development of general-purpose MLIPs, by introducing GAIA, an end-to-end framework to build a wide range of atomic arrangements. By employing systematic evaluation of metadynamics for effective structural exploration, GAIA overcomes the heuristic nature of conventional dataset generation. Using GAIA, we constructed Titan25, a benchmark-scale dataset, and trained MLIPs that closely match both static and dynamic density functional theory results. The models further reproduce experimental observations across reactive regimes, including detonation, coalescence, and catalytic activity. GAIA narrows the gap between experiment and simulation, and paves the way for the development of universal MLIPs that can reliably describe a wide spectrum of materials and chemical processes.

We introduce a machine learning model to predict atomization energies of a diverse set of organic molecules, based on nuclear charges and atomic positions only. The problem of solving the molecular Schrödinger equation is mapped onto a non-linear statistical regression problem of reduced complexity. Regression models are trained on and compared to atomization energies computed with hybrid density-functional theory. Cross-validation over more than seven thousand small organic molecules yields a mean absolute error of ~10 kcal/mol. Applicability is demonstrated for the prediction of molecular atomization potential energy curves.

Machine-learned interatomic potentials are revolutionising atomistic materials simulations by providing accurate and scalable predictions within the scope covered by the training data. However, generation of an accurate and robust training data set remains a challenge, often requiring thousands of first-principles calculations to achieve high accuracy. Foundation models have started to emerge with the ambition to create universally applicable potentials across a wide range of materials. While foundation models can be robust and transferable, they do not yet achieve the accuracy required to predict reaction barriers, phase transitions, and material stability. This work demonstrates that foundation model potentials can reach chemical accuracy when fine-tuned using transfer learning with partially frozen weights and biases. For two challenging datasets on reactive chemistry at surfaces and stability and elastic properties of tertiary alloys, we show that frozen transfer learning with 10-20% of the data (hundreds of datapoints) achieves similar accuracies to models trained from scratch (on thousands of datapoints). Moreover, we show that an equally accurate, but significantly more efficient surrogate model can be built using the transfer learned potential as the ground truth. In combination, we present a simulation workflow for machine learning potentials that improves data efficiency and computational efficiency.

Computational quantum chemistry plays a critical role in drug discovery, chemical synthesis, and materials science. While first-principles methods, such as density functional theory (DFT), provide high accuracy in modeling electronic structures and predicting molecular properties, they are computationally expensive. Machine learning interatomic potentials (MLIPs) have emerged as promising surrogate models that aim to achieve DFT-level accuracy while enabling efficient large-scale atomistic simulations. The development of accurate and transferable MLIPs requires large-scale, high-quality datasets with both energy and force labels. Critically, MLIPs must generalize not only to stable geometries but also to intermediate, non-equilibrium conformations encountered during atomistic simulations. In this work, we introduce PubChemQCR, a large-scale dataset of molecular relaxation trajectories curated from the raw geometry optimization outputs of the PubChemQC project. PubChemQCR is the largest publicly available dataset of DFT-based relaxation trajectories for small organic molecules, comprising approximately 3.5 million trajectories and over 300 million molecular conformations computed at various levels of theory. Each conformation is labeled with both total energy and atomic forces, making the dataset suitable for training and evaluating MLIPs. To provide baselines for future developments, we benchmark nine representative MLIP models on the dataset. Our resources are publicly available at https://huggingface.co/divelab

Computational methods that operate on three-dimensional molecular structure have the potential to solve important questions in biology and chemistry. In particular, deep neural networks have gained significant attention, but their widespread adoption in the biomolecular domain has been limited by a lack of either systematic performance benchmarks or a unified toolkit for interacting with molecular data. To address this, we present ATOM3D, a collection of both novel and existing benchmark datasets spanning several key classes of biomolecules. We implement several classes of three-dimensional molecular learning methods for each of these tasks and show that they consistently improve performance relative to methods based on one- and two-dimensional representations. The specific choice of architecture proves to be critical for performance, with three-dimensional convolutional networks excelling at tasks involving complex geometries, graph networks performing well on systems requiring detailed positional information, and the more recently developed equivariant networks showing significant promise. Our results indicate that many molecular problems stand to gain from three-dimensional molecular learning, and that there is potential for improvement on many tasks which remain underexplored. To lower the barrier to entry and facilitate further developments in the field, we also provide a comprehensive suite of tools for dataset processing, model training, and evaluation in our open-source atom3d Python package. All datasets are available for download from https://www.atom3d.ai .

Modern materials science has historically been founded on combining restricted subsets of the periodic table, favoring high-purity, few-element systems. However, the demands of an emerging circular economy, together with the need to understand materials behavior under planetary and industrial extremes, increasingly require mastering Mendeleev materials - chemically and structurally complex systems that span large portions of the periodic table. In these regimes, current universal machine-learning interatomic potentials often fail, largely due to systematic gaps in traditional training datasets that heavily emphasize low-energy, near-equilibrium structures. We address this limitation by introducing a chemistry-agnostic, information-entropy-maximization protocol for data generation. By decoupling structural sampling from thermodynamic bias, our approach provides a robust physical prior for atomic interactions across the entire periodic table, including regimes far from equilibrium and under extreme conditions. Training a Graph Atomic Cluster Expansion (GRACE) model on the resulting statistically maximized entropy (SMAX) dataset yields markedly improved robustness across a range of stringent benchmarks. These include large-strain phase transformations in tin, defect evolution in tungsten-based alloys, and catalytic reaction barrier prediction. More broadly, our approach establishes a scalable and principled methodology for navigating the vast chemical and configurational space relevant to future materials design. It enables a paradigm of discovery by simulation in which unbiased sampling protocols autonomously resolve emergent structures in multi-elemental mixtures-such as systems containing the nine most abundant elements in the Earth's crust-without reliance on a priori chemical assumptions.

The development of efficient machine learning models for molecular systems representation is becoming crucial in scientific research. We introduce TensorNet, an innovative O(3)-equivariant message-passing neural network architecture that leverages Cartesian tensor representations. By using Cartesian tensor atomic embeddings, feature mixing is simplified through matrix product operations. Furthermore, the cost-effective decomposition of these tensors into rotation group irreducible representations allows for the separate processing of scalars, vectors, and tensors when necessary. Compared to higher-rank spherical tensor models, TensorNet demonstrates state-of-the-art performance with significantly fewer parameters. For small molecule potential energies, this can be achieved even with a single interaction layer. As a result of all these properties, the model's computational cost is substantially decreased. Moreover, the accurate prediction of vector and tensor molecular quantities on top of potential energies and forces is possible. In summary, TensorNet's framework opens up a new space for the design of state-of-the-art equivariant models.

Density Functional Theory (DFT) underpins much of modern computational chemistry and materials science. Yet, the reliability of DFT-derived predictions of experimentally measurable properties remains fundamentally limited by the need to approximate the unknown exchange-correlation (XC) functional. The traditional paradigm for improving accuracy has relied on increasingly elaborate hand-crafted functional forms. This approach has led to a longstanding trade-off between computational efficiency and accuracy, which remains insufficient for reliable predictive modelling of laboratory experiments. Here we introduce Skala, a deep learning-based XC functional that surpasses state-of-the-art hybrid functionals in accuracy across the main-group chemistry benchmark set GMTKN55 with an error of 2.8 kcal/mol, while retaining the lower computational cost characteristic of semi-local DFT. This demonstrated departure from the historical trade-off between accuracy and efficiency is enabled by learning non-local representations of electronic structure directly from data, bypassing the need for increasingly costly hand-engineered features. Leveraging an unprecedented volume of high-accuracy reference data from wavefunction-based methods, we establish that modern deep learning enables systematically improvable neural exchange-correlation models as training datasets expand, positioning first-principles simulations to become progressively more predictive.

The efficient exploration of chemical space to design molecules with intended properties enables the accelerated discovery of drugs, materials, and catalysts, and is one of the most important outstanding challenges in chemistry. Encouraged by the recent surge in computer power and artificial intelligence development, many algorithms have been developed to tackle this problem. However, despite the emergence of many new approaches in recent years, comparatively little progress has been made in developing realistic benchmarks that reflect the complexity of molecular design for real-world applications. In this work, we develop a set of practical benchmark tasks relying on physical simulation of molecular systems mimicking real-life molecular design problems for materials, drugs, and chemical reactions. Additionally, we demonstrate the utility and ease of use of our new benchmark set by demonstrating how to compare the performance of several well-established families of algorithms. Surprisingly, we find that model performance can strongly depend on the benchmark domain. We believe that our benchmark suite will help move the field towards more realistic molecular design benchmarks, and move the development of inverse molecular design algorithms closer to designing molecules that solve existing problems in both academia and industry alike.

Generating the periodic structure of stable materials is a long-standing challenge for the material design community. This task is difficult because stable materials only exist in a low-dimensional subspace of all possible periodic arrangements of atoms: 1) the coordinates must lie in the local energy minimum defined by quantum mechanics, and 2) global stability also requires the structure to follow the complex, yet specific bonding preferences between different atom types. Existing methods fail to incorporate these factors and often lack proper invariances. We propose a Crystal Diffusion Variational Autoencoder (CDVAE) that captures the physical inductive bias of material stability. By learning from the data distribution of stable materials, the decoder generates materials in a diffusion process that moves atomic coordinates towards a lower energy state and updates atom types to satisfy bonding preferences between neighbors. Our model also explicitly encodes interactions across periodic boundaries and respects permutation, translation, rotation, and periodic invariances. We significantly outperform past methods in three tasks: 1) reconstructing the input structure, 2) generating valid, diverse, and realistic materials, and 3) generating materials that optimize a specific property. We also provide several standard datasets and evaluation metrics for the broader machine learning community.

The simulation of large-scale systems with complex electron interactions remains one of the greatest challenges for the atomistic modeling of materials. Although classical force fields often fail to describe the coupling between electronic states and ionic rearrangements, the more accurate ab-initio molecular dynamics suffers from computational complexity that prevents long-time and large-scale simulations, which are essential to study many technologically relevant phenomena, such as reactions, ion migrations, phase transformations, and degradation. In this work, we present the Crystal Hamiltonian Graph neural Network (CHGNet) as a novel machine-learning interatomic potential (MLIP), using a graph-neural-network-based force field to model a universal potential energy surface. CHGNet is pretrained on the energies, forces, stresses, and magnetic moments from the Materials Project Trajectory Dataset, which consists of over 10 years of density functional theory static and relaxation trajectories of sim 1.5 million inorganic structures. The explicit inclusion of magnetic moments enables CHGNet to learn and accurately represent the orbital occupancy of electrons, enhancing its capability to describe both atomic and electronic degrees of freedom. We demonstrate several applications of CHGNet in solid-state materials, including charge-informed molecular dynamics in Li_xMnO_2, the finite temperature phase diagram for Li_xFePO_4 and Li diffusion in garnet conductors. We critically analyze the significance of including charge information for capturing appropriate chemistry, and we provide new insights into ionic systems with additional electronic degrees of freedom that can not be observed by previous MLIPs.

Crystals are the foundation of numerous scientific and industrial applications. While various learning-based approaches have been proposed for crystal generation, existing methods seldom consider the space group constraint which is crucial in describing the geometry of crystals and closely relevant to many desirable properties. However, considering space group constraint is challenging owing to its diverse and nontrivial forms. In this paper, we reduce the space group constraint into an equivalent formulation that is more tractable to be handcrafted into the generation process. In particular, we translate the space group constraint into two parts: the basis constraint of the invariant logarithmic space of the lattice matrix and the Wyckoff position constraint of the fractional coordinates. Upon the derived constraints, we then propose DiffCSP++, a novel diffusion model that has enhanced a previous work DiffCSP by further taking space group constraint into account. Experiments on several popular datasets verify the benefit of the involvement of the space group constraint, and show that our DiffCSP++ achieves promising performance on crystal structure prediction, ab initio crystal generation and controllable generation with customized space groups.

Accurate modelling of electrostatic interactions and charge transfer is fundamental to computational chemistry, yet most machine learning interatomic potentials (MLIPs) rely on local atomic descriptors that cannot capture long-range electrostatic effects. We present a new electrostatic foundation model for molecular chemistry that extends the MACE architecture with explicit treatment of long-range interactions and electrostatic induction. Our approach combines local many-body geometric features with a non-self-consistent field formalism that updates learnable charge and spin densities through polarisable iterations to model induction, followed by global charge equilibration via learnable Fukui functions to control total charge and total spin. This design enables an accurate and physical description of systems with varying charge and spin states while maintaining computational efficiency. Trained on the OMol25 dataset of 100 million hybrid DFT calculations, our models achieve chemical accuracy across diverse benchmarks, with accuracy competitive with hybrid DFT on thermochemistry, reaction barriers, conformational energies, and transition metal complexes. Notably, we demonstrate that the inclusion of long-range electrostatics leads to a large improvement in the description of non-covalent interactions and supramolecular complexes over non-electrostatic models, including sub-kcal/mol prediction of molecular crystal formation energy in the X23-DMC dataset and a fourfold improvement over short-ranged models on protein-ligand interactions. The model's ability to handle variable charge and spin states, respond to external fields, provide interpretable spin-resolved charge densities, and maintain accuracy from small molecules to protein-ligand complexes positions it as a versatile tool for computational molecular chemistry and drug discovery.

Large-amplitude molecular motions which occur during isomerization can cause significant changes in electronic structure. These variations in electronic properties can be used to identify vibrationally-excited eigenstates which are localized along the potential energy surface. This work demonstrates that nuclear quadrupole hyperfine interactions can be used as a diagnostic marker of progress along the isomerization path in both the HC14N/H14NC and DC15N/D15NC chemical systems. Ab initio calculations at the CCSD(T)/cc-pCVQZ level indicate that the hyperfine interaction is extremely sensitive to the chemical bonding of the quadrupolar 14N nucleus and can therefore be used to determine in which potential well the vibrational wavefunction is localized. A natural bonding orbital analysis along the isomerization path further demonstrates that hyperfine interactions arise from the asphericity of the electron density at the quadrupolar nucleus. Using the CCSD(T) potential surface, the quadrupole coupling constants of highly-excited vibrational states are computed from a one-dimensional internal coordinate path Hamiltonian. The excellent agreement between ab initio calculations and recent measurements demonstrates that nuclear quadrupole hyperfine structure can be used as a diagnostic tool for characterizing localized HCN and HNC vibrational states.

Molecular dynamics simulation of plasma-surface interactions requires an interatomic potential that is simultaneously accurate, computationally efficient, and able to describe many elements and bonding types in reactive systems. In principle, a foundation model for machine-learned interatomic potential (MLIP) can meet these demands. We explore the use of the Universal Models for Atoms (UMA) model, developed by Meta FAIR, for the interactions of oxygen plasma species on a multilayer of WS_2, a promising 2D material. Starting from the pretrained uma-s-1p1 model under the Open Catalyst 2020 (OC20) task, we apply an iterative fine-tuning loop with maximally diverse configuration sampling using Smooth Overlap of Atomic Positions (SOAP) and Farthest Point Sampling (FPS); DFT labeling at the PBE+D3+U+spin level; and fine-tuning on energy, force, and stress labels. Even in the absence of fine-tuning, the pretrained model reproduces the production-scale observables of interest, namely, chemisorbed S and O coverage under 15eV O^+ and O_2^+ bombardment. These results were obtained without spin polarization and Hubbard U correction. Nonetheless, fine-tuning reduces the energy and force mean absolute error (MAE) to 4.5times10^{-3}eV/atom and 0.076eV/angstrom, respectively.

Catalyst discovery and optimization is key to solving many societal and energy challenges including solar fuels synthesis, long-term energy storage, and renewable fertilizer production. Despite considerable effort by the catalysis community to apply machine learning models to the computational catalyst discovery process, it remains an open challenge to build models that can generalize across both elemental compositions of surfaces and adsorbate identity/configurations, perhaps because datasets have been smaller in catalysis than related fields. To address this we developed the OC20 dataset, consisting of 1,281,040 Density Functional Theory (DFT) relaxations (~264,890,000 single point evaluations) across a wide swath of materials, surfaces, and adsorbates (nitrogen, carbon, and oxygen chemistries). We supplemented this dataset with randomly perturbed structures, short timescale molecular dynamics, and electronic structure analyses. The dataset comprises three central tasks indicative of day-to-day catalyst modeling and comes with pre-defined train/validation/test splits to facilitate direct comparisons with future model development efforts. We applied three state-of-the-art graph neural network models (CGCNN, SchNet, Dimenet++) to each of these tasks as baseline demonstrations for the community to build on. In almost every task, no upper limit on model size was identified, suggesting that even larger models are likely to improve on initial results. The dataset and baseline models are both provided as open resources, as well as a public leader board to encourage community contributions to solve these important tasks.

Obtaining the desired effect of drugs is highly dependent on their molecular geometries. Thus, the current prevailing paradigm focuses on 3D point-cloud atom representations, utilizing graph neural network (GNN) parametrizations, with rotational symmetries baked in via E(3) invariant layers. We prove that such models must necessarily disregard chirality, a geometric property of the molecules that cannot be superimposed on their mirror image by rotation and translation. Chirality plays a key role in determining drug safety and potency. To address this glaring issue, we introduce a novel field-based representation, proposing reference rotations that replace rotational symmetry constraints. The proposed model captures all molecular geometries including chirality, while still achieving highly competitive performance with E(3)-based methods across standard benchmarking metrics.

Large-scale datasets have enabled highly accurate machine learning interatomic potentials (MLIPs) for general-purpose heterogeneous catalysis modeling. There are, however, some limitations in what can be treated with these potentials because of gaps in the underlying training data. To extend these capabilities, we introduce AQCat25, a complementary dataset of 13.5 million density functional theory (DFT) single point calculations designed to improve the treatment of systems where spin polarization and/or higher fidelity are critical. We also investigate methodologies for integrating new datasets, such as AQCat25, with the broader Open Catalyst 2020 (OC20) dataset to create spin-aware models without sacrificing generalizability. We find that directly tuning a general model on AQCat25 leads to catastrophic forgetting of the original dataset's knowledge. Conversely, joint training strategies prove effective for improving accuracy on the new data without sacrificing general performance. This joint approach introduces a challenge, as the model must learn from a dataset containing both mixed-fidelity calculations and mixed-physics (spin-polarized vs. unpolarized). We show that explicitly conditioning the model on this system-specific metadata, for example by using Feature-wise Linear Modulation (FiLM), successfully addresses this challenge and further enhances model accuracy. Ultimately, our work establishes an effective protocol for bridging DFT fidelity domains to advance the predictive power of foundational models in catalysis.

We extend molecular bootstrap embedding to make it appropriate for implementation on a quantum computer. This enables solution of the electronic structure problem of a large molecule as an optimization problem for a composite Lagrangian governing fragments of the total system, in such a way that fragment solutions can harness the capabilities of quantum computers. By employing state-of-art quantum subroutines including the quantum SWAP test and quantum amplitude amplification, we show how a quadratic speedup can be obtained over the classical algorithm, in principle. Utilization of quantum computation also allows the algorithm to match -- at little additional computational cost -- full density matrices at fragment boundaries, instead of being limited to 1-RDMs. Current quantum computers are small, but quantum bootstrap embedding provides a potentially generalizable strategy for harnessing such small machines through quantum fragment matching.

Compound identification and structure annotation from mass spectra is a well-established task widely applied in drug detection, criminal forensics, small molecule biomarker discovery and chemical engineering. We propose SpecTUS: Spectral Translator for Unknown Structures, a deep neural model that addresses the task of structural annotation of small molecules from low-resolution gas chromatography electron ionization mass spectra (GC-EI-MS). Our model analyzes the spectra in de novo manner -- a direct translation from the spectra into 2D-structural representation. Our approach is particularly useful for analyzing compounds unavailable in spectral libraries. In a rigorous evaluation of our model on the novel structure annotation task across different libraries, we outperformed standard database search techniques by a wide margin. On a held-out testing set, including 28267 spectra from the NIST database, we show that our model's single suggestion perfectly reconstructs 43\% of the subset's compounds. This single suggestion is strictly better than the candidate of the database hybrid search (common method among practitioners) in 76\% of cases. In a~still affordable scenario of~10 suggestions, perfect reconstruction is achieved in 65\%, and 84\% are better than the hybrid search.

Recent advances in molecular foundation models have shown impressive performance in molecular property prediction and de novo molecular design, with promising applications in areas such as drug discovery and reaction prediction. Nevertheless, most existing approaches rely exclusively on SMILES representations and overlook both experimental spectra and 3D structural information-two indispensable sources for capturing molecular behavior in real-world scenarios. This limitation reduces their effectiveness in tasks where stereochemistry, spatial conformation, and experimental validation are critical. To overcome these challenges, we propose MolSpectLLM, a molecular foundation model pretrained on Qwen2.5-7B that unifies experimental spectroscopy with molecular 3D structure. By explicitly modeling molecular spectra, MolSpectLLM achieves state-of-the-art performance on spectrum-related tasks, with an average accuracy of 0.53 across NMR, IR, and MS benchmarks. MolSpectLLM also shows strong performance on the spectra analysis task, obtaining 15.5% sequence accuracy and 41.7% token accuracy on Spectra-to-SMILES, substantially outperforming large general-purpose LLMs. More importantly, MolSpectLLM not only achieves strong performance on molecular elucidation tasks, but also generates accurate 3D molecular structures directly from SMILES or spectral inputs, bridging spectral analysis, molecular elucidation, and molecular design. Code are available at https://github.com/Eurekashen/MolSpectLLM{https://github.com/Eurekashen/MolSpectLLM}.

Identifying transition states (TSs) on potential energy surfaces is a central computational bottleneck in mechanistic studies of catalytic materials. A TS search is not a single calculation but a long-horizon, multi-step workflow of atomistic simulations with delayed, asynchronous feedback and heterogeneous failure modes that require a joint multimodal analysis of scalar convergence diagnostics and atomic geometries along the reaction path. To address this challenge, we propose TSAgent, an agentic workflow that automates TS search directly at the density functional theory (DFT) level of quantum chemical accuracy. TSAgent operates through a persistent plan-execute-analyze-replan loop, continuously adapting its strategy based on convergence diagnostics and geometric feedback without human intervention. We evaluate TSAgent on a diverse 100-example subset of the OC20NEB heterogeneous catalysis benchmark, where it successfully locates TSs with 83% accuracy. In a direct comparison against expert DFT practitioners on 10 held-out examples, TSAgent achieves a 70% success rate compared to a human-expert average of 73 +/- 12%. Finally, TSAgent independently reproduces Bronsted-Evans-Polanyi scaling relationships for NH3 dissociation on metal and single-atom alloy surfaces from a published heterogeneous catalysis study, demonstrating that its utility extends beyond curated benchmarks to real scientific investigations.

Extended-connectivity fingerprints (ECFPs) are a ubiquitous tool in current cheminformatics and molecular machine learning, and one of the most prevalent molecular feature extraction techniques used for chemical prediction. Atom features learned by graph neural networks can be aggregated to compound-level representations using a large spectrum of graph pooling methods; in contrast, sets of detected ECFP substructures are by default transformed into bit vectors using only a simple hash-based folding procedure. We introduce a general mathematical framework for the vectorisation of structural fingerprints via a formal operation called substructure pooling that encompasses hash-based folding, algorithmic substructure-selection, and a wide variety of other potential techniques. We go on to describe Sort & Slice, an easy-to-implement and bit-collision-free alternative to hash-based folding for the pooling of ECFP substructures. Sort & Slice first sorts ECFP substructures according to their relative prevalence in a given set of training compounds and then slices away all but the L most frequent substructures which are subsequently used to generate a binary fingerprint of desired length, L. We computationally compare the performance of hash-based folding, Sort & Slice, and two advanced supervised substructure-selection schemes (filtering and mutual-information maximisation) for ECFP-based molecular property prediction. Our results indicate that, despite its technical simplicity, Sort & Slice robustly (and at times substantially) outperforms traditional hash-based folding as well as the other investigated methods across prediction tasks, data splitting techniques, machine-learning models and ECFP hyperparameters. We thus recommend that Sort & Slice canonically replace hash-based folding as the default substructure-pooling technique to vectorise ECFPs for supervised molecular machine learning.

Molecular representation is a foundational element in our understanding of the physical world. Its importance ranges from the fundamentals of chemical reactions to the design of new therapies and materials. Previous molecular machine learning models have employed strings, fingerprints, global features, and simple molecular graphs that are inherently information-sparse representations. However, as the complexity of prediction tasks increases, the molecular representation needs to encode higher fidelity information. This work introduces a novel approach to infusing quantum-chemical-rich information into molecular graphs via stereoelectronic effects. We show that the explicit addition of stereoelectronic interactions significantly improves the performance of molecular machine learning models. Furthermore, stereoelectronics-infused representations can be learned and deployed with a tailored double graph neural network workflow, enabling its application to any downstream molecular machine learning task. Finally, we show that the learned representations allow for facile stereoelectronic evaluation of previously intractable systems, such as entire proteins, opening new avenues of molecular design.

We aim to learn wavefunctions simulated by time-dependent density functional theory (TDDFT), which can be efficiently represented as linear combination coefficients of atomic orbitals. In real-time TDDFT, the electronic wavefunctions of a molecule evolve over time in response to an external excitation, enabling first-principles predictions of physical properties such as optical absorption, electron dynamics, and high-order response. However, conventional real-time TDDFT relies on time-consuming propagation of all occupied states with fine time steps. In this work, we propose OrbEvo, which is based on an equivariant graph transformer architecture and learns to evolve the full electronic wavefunction coefficients across time steps. First, to account for external field, we design an equivariant conditioning to encode both strength and direction of external electric field and break the symmetry from SO(3) to SO(2). Furthermore, we design two OrbEvo models, OrbEvo-WF and OrbEvo-DM, using wavefunction pooling and density matrix as interaction method, respectively. Motivated by the central role of the density functional in TDDFT, OrbEvo-DM encodes the density matrix aggregated from all occupied electronic states into feature vectors via tensor contraction, providing a more intuitive approach to learn the time evolution operator. We adopt a training strategy specifically tailored to limit the error accumulation of time-dependent wavefunctions over autoregressive rollout. To evaluate our approach, we generate TDDFT datasets consisting of 5,000 different molecules in the QM9 dataset and 1,500 molecular configurations of the malonaldehyde molecule in the MD17 dataset. Results show that our OrbEvo model accurately captures quantum dynamics of excited states under external field, including time-dependent wavefunctions, time-dependent dipole moment, and optical absorption spectra.

Identifying useful sorbent materials for direct air capture (DAC) from humid air remains a challenge. We present the Open DAC 2025 (ODAC25) dataset, a significant expansion and improvement upon ODAC23 (Sriram et al., ACS Central Science, 10 (2024) 923), comprising nearly 70 million DFT single-point calculations for CO_2, H_2O, N_2, and O_2 adsorption in 15,000 MOFs. ODAC25 introduces chemical and configurational diversity through functionalized MOFs, high-energy GCMC-derived placements, and synthetically generated frameworks. ODAC25 also significantly improves upon the accuracy of DFT calculations and the treatment of flexible MOFs in ODAC23. Along with the dataset, we release new state-of-the-art machine-learned interatomic potentials trained on ODAC25 and evaluate them on adsorption energy and Henry's law coefficient predictions.

Designing metal-organic frameworks (MOFs) with novel chemistries is a longstanding challenge due to their large combinatorial space and complex 3D arrangements of the building blocks. While recent deep generative models have enabled scalable MOF generation, they assume (1) a fixed set of building blocks and (2) known local 3D coordinates of building blocks. However, this limits their ability to (1) design novel MOFs and (2) generate the structure using novel building blocks. We propose a two-stage MOF generation framework that overcomes these limitations by modeling both chemical and geometric degrees of freedom. First, we train an SMILES-based autoregressive model to generate metal and organic building blocks, paired with a cheminformatics toolkit for 3D structure initialization. Second, we introduce a flow matching model that predicts translations, rotations, and torsional angles to assemble the blocks into valid 3D frameworks. Our experiments demonstrate improved reconstruction accuracy, the generation of valid, novel, and unique MOFs, and the ability to create novel building blocks. Our code is available at https://github.com/nayoung10/MOFFlow-2.

The presence of point defects such as vacancies plays an important role in material design. Here, we demonstrate that a graph neural network (GNN) model trained only on perfect materials can also be used to predict vacancy formation energies (E_{vac}) of defect structures without the need for additional training data. Such GNN-based predictions are considerably faster than density functional theory (DFT) calculations with reasonable accuracy and show the potential that GNNs are able to capture a functional form for energy predictions. To test this strategy, we developed a DFT dataset of 508 E_{vac} consisting of 3D elemental solids, alloys, oxides, nitrides, and 2D monolayer materials. We analyzed and discussed the applicability of such direct and fast predictions. We applied the model to predict 192494 E_{vac} for 55723 materials in the JARVIS-DFT database.

Generative Flow Networks (GFlowNets) have recently emerged as a suitable framework for generating diverse and high-quality molecular structures by learning from rewards treated as unnormalized distributions. Previous works in this framework often restrict exploration by using predefined molecular fragments as building blocks, limiting the chemical space that can be accessed. In this work, we introduce Atomic GFlowNets (A-GFNs), a foundational generative model leveraging individual atoms as building blocks to explore drug-like chemical space more comprehensively. We propose an unsupervised pre-training approach using drug-like molecule datasets, which teaches A-GFNs about inexpensive yet informative molecular descriptors such as drug-likeliness, topological polar surface area, and synthetic accessibility scores. These properties serve as proxy rewards, guiding A-GFNs towards regions of chemical space that exhibit desirable pharmacological properties. We further implement a goal-conditioned finetuning process, which adapts A-GFNs to optimize for specific target properties. In this work, we pretrain A-GFN on a subset of ZINC dataset, and by employing robust evaluation metrics we show the effectiveness of our approach when compared to other relevant baseline methods for a wide range of drug design tasks. The code is accessible at https://github.com/diamondspark/AGFN.

Establishing the relationship between 3D structures and the energy states of molecular systems has proven to be a promising approach for learning 3D molecular representations. However, existing methods are limited to modeling the molecular energy states from classical mechanics. This limitation results in a significant oversight of quantum mechanical effects, such as quantized (discrete) energy level structures, which offer a more accurate estimation of molecular energy and can be experimentally measured through energy spectra. In this paper, we propose to utilize the energy spectra to enhance the pre-training of 3D molecular representations (MolSpectra), thereby infusing the knowledge of quantum mechanics into the molecular representations. Specifically, we propose SpecFormer, a multi-spectrum encoder for encoding molecular spectra via masked patch reconstruction. By further aligning outputs from the 3D encoder and spectrum encoder using a contrastive objective, we enhance the 3D encoder's understanding of molecules. Evaluations on public benchmarks reveal that our pre-trained representations surpass existing methods in predicting molecular properties and modeling dynamics.

Machine learning force fields (MLFF) have been proposed to accelerate molecular dynamics (MD) simulation, which finds widespread applications in chemistry and biomedical research. Even for the most data-efficient MLFFs, reaching chemical accuracy can require hundreds of frames of force and energy labels generated by expensive quantum mechanical algorithms, which may scale as O(n^3) to O(n^7), with n proportional to the number of basis functions. To address this issue, we propose a multi-stage computational framework -- ASTEROID, which lowers the data cost of MLFFs by leveraging a combination of cheap inaccurate data and expensive accurate data. The motivation behind ASTEROID is that inaccurate data, though incurring large bias, can help capture the sophisticated structures of the underlying force field. Therefore, we first train a MLFF model on a large amount of inaccurate training data, employing a bias-aware loss function to prevent the model from overfitting tahe potential bias of this data. We then fine-tune the obtained model using a small amount of accurate training data, which preserves the knowledge learned from the inaccurate training data while significantly improving the model's accuracy. Moreover, we propose a variant of ASTEROID based on score matching for the setting where the inaccurate training data are unlabeled. Extensive experiments on MD datasets and downstream tasks validate the efficacy of ASTEROID. Our code and data are available at https://github.com/abukharin3/asteroid.

Crystalline materials are a fundamental component in next-generation technologies, yet modeling their distribution presents unique computational challenges. Of the plausible arrangements of atoms in a periodic lattice only a vanishingly small percentage are thermodynamically stable, which is a key indicator of the materials that can be experimentally realized. Two fundamental tasks in this area are to (a) predict the stable crystal structure of a known composition of elements and (b) propose novel compositions along with their stable structures. We present FlowMM, a pair of generative models that achieve state-of-the-art performance on both tasks while being more efficient and more flexible than competing methods. We generalize Riemannian Flow Matching to suit the symmetries inherent to crystals: translation, rotation, permutation, and periodic boundary conditions. Our framework enables the freedom to choose the flow base distributions, drastically simplifying the problem of learning crystal structures compared with diffusion models. In addition to standard benchmarks, we validate FlowMM's generated structures with quantum chemistry calculations, demonstrating that it is about 3x more efficient, in terms of integration steps, at finding stable materials compared to previous open methods.

Graph Neural Networks (GNNs) have been widely adopted for drug discovery with molecular graphs. Nevertheless, current GNNs are mainly good at leveraging short-range interactions (SRI) but struggle to capture long-range interactions (LRI), both of which are crucial for determining molecular properties. To tackle this issue, we propose a method that implicitly projects all original atoms into a few Neural Atoms, which abstracts the collective information of atomic groups within a molecule. Specifically, we explicitly exchange the information among neural atoms and project them back to the atoms' representations as an enhancement. With this mechanism, neural atoms establish the communication channels among distant nodes, effectively reducing the interaction scope of arbitrary node pairs into a single hop. To provide an inspection of our method from a physical perspective, we reveal its connection with the traditional LRI calculation method, Ewald Summation. We conduct extensive experiments on three long-range graph benchmarks, covering both graph-level and link-level tasks on molecular graphs. We empirically justify that our method can be equipped with an arbitrary GNN and help to capture LRI.

Scaling has been critical in improving model performance and generalization in machine learning. It involves how a model's performance changes with increases in model size or input data, as well as how efficiently computational resources are utilized to support this growth. Despite successes in other areas, the study of scaling in Neural Network Interatomic Potentials (NNIPs) remains limited. NNIPs act as surrogate models for ab initio quantum mechanical calculations. The dominant paradigm here is to incorporate many physical domain constraints into the model, such as rotational equivariance. We contend that these complex constraints inhibit the scaling ability of NNIPs, and are likely to lead to performance plateaus in the long run. In this work, we take an alternative approach and start by systematically studying NNIP scaling strategies. Our findings indicate that scaling the model through attention mechanisms is efficient and improves model expressivity. These insights motivate us to develop an NNIP architecture designed for scalability: the Efficiently Scaled Attention Interatomic Potential (EScAIP). EScAIP leverages a multi-head self-attention formulation within graph neural networks, applying attention at the neighbor-level representations. Implemented with highly-optimized attention GPU kernels, EScAIP achieves substantial gains in efficiency--at least 10x faster inference, 5x less memory usage--compared to existing NNIPs. EScAIP also achieves state-of-the-art performance on a wide range of datasets including catalysts (OC20 and OC22), molecules (SPICE), and materials (MPTrj). We emphasize that our approach should be thought of as a philosophy rather than a specific model, representing a proof-of-concept for developing general-purpose NNIPs that achieve better expressivity through scaling, and continue to scale efficiently with increased computational resources and training data.

Point defects play a central role in driving the properties of materials. First-principles methods are widely used to compute defect energetics and structures, including at scale for high-throughput defect databases. However, these methods are computationally expensive, making machine-learning force fields (MLFFs) an attractive alternative for accelerating structural relaxations. Most existing MLFFs are based on graph neural networks (GNNs), which can suffer from oversmoothing and poor representation of long-range interactions. Both of these issues are especially of concern when modeling point defects. To address these challenges, we introduce the Accelerated Deep Atomic Potential Transformer (ADAPT), an MLFF that replaces graph representations with a direct coordinates-in-space formulation and explicitly considers all pairwise atomic interactions. Atoms are treated as tokens, with a Transformer encoder modeling their interactions. Applied to a dataset of silicon point defects, ADAPT achieves a roughly 33 percent reduction in both force and energy prediction errors relative to a state-of-the-art GNN-based model, while requiring only a fraction of the computational cost.

Molecular pretrained representations (MPR) has emerged as a powerful approach for addressing the challenge of limited supervised data in applications such as drug discovery and material design. While early MPR methods relied on 1D sequences and 2D graphs, recent advancements have incorporated 3D conformational information to capture rich atomic interactions. However, these prior models treat molecules merely as discrete atom sets, overlooking the space surrounding them. We argue from a physical perspective that only modeling these discrete points is insufficient. We first present a simple yet insightful observation: naively adding randomly sampled virtual points beyond atoms can surprisingly enhance MPR performance. In light of this, we propose a principled framework that incorporates the entire 3D space spanned by molecules. We implement the framework via a novel Transformer-based architecture, dubbed SpaceFormer, with three key components: (1) grid-based space discretization; (2) grid sampling/merging; and (3) efficient 3D positional encoding. Extensive experiments show that SpaceFormer significantly outperforms previous 3D MPR models across various downstream tasks with limited data, validating the benefit of leveraging the additional 3D space beyond atoms in MPR models.

SO(3)-equivariant networks are the dominant models for machine learning interatomic potentials (MLIPs). The key operation of such networks is the Clebsch-Gordan (CG) tensor product, which is computationally expensive. To accelerate the computation, we develop tensor decomposition networks (TDNs) as a class of approximately equivariant networks in which CG tensor products are replaced by low-rank tensor decompositions, such as the CANDECOMP/PARAFAC (CP) decomposition. With the CP decomposition, we prove (i) a uniform bound on the induced error of SO(3)-equivariance, and (ii) the universality of approximating any equivariant bilinear map. To further reduce the number of parameters, we propose path-weight sharing that ties all multiplicity-space weights across the O(L^3) CG paths into a single shared parameter set without compromising equivariance, where L is the maximum angular degree. The resulting layer acts as a plug-and-play replacement for tensor products in existing networks, and the computational complexity of tensor products is reduced from O(L^6) to O(L^4). We evaluate TDNs on PubChemQCR, a newly curated molecular relaxation dataset containing 105 million DFT-calculated snapshots. We also use existing datasets, including OC20, and OC22. Results show that TDNs achieve competitive performance with dramatic speedup in computations. Our code is publicly available as part of the AIRS library (https://github.com/divelab/AIRS/tree/main/OpenMol/TDN{https://github.com/divelab/AIRS/}).

Fundamental tasks in computational chemistry, from transition state search to vibrational analysis, rely on molecular Hessians, which are the second derivatives of the potential energy. Yet, Hessians are computationally expensive to calculate and scale poorly with system size, with both quantum mechanical methods and neural networks. In this work, we demonstrate that Hessians can be predicted directly from a deep learning model, without relying on automatic differentiation or finite differences. We observe that one can construct SE(3)-equivariant, symmetric Hessians from irreducible representations (irrep) features up to degree l=2 computed during message passing in graph neural networks. This makes HIP Hessians one to two orders of magnitude faster, more accurate, more memory efficient, easier to train, and enables more favorable scaling with system size. We validate our predictions across a wide range of downstream tasks, demonstrating consistently superior performance for transition state search, accelerated geometry optimization, zero-point energy corrections, and vibrational analysis benchmarks. We open-source the HIP codebase and model weights to enable further development of the direct prediction of Hessians at https://github.com/BurgerAndreas/hip

Chemical transport models (CTMs), which simulate air pollution transport, transformation, and removal, are computationally expensive, largely because of the computational intensity of the chemical mechanisms: systems of coupled differential equations representing atmospheric chemistry. Here we investigate the potential for machine learning to reproduce the behavior of a chemical mechanism, yet with reduced computational expense. We create a 17-layer residual multi-target regression neural network to emulate the Carbon Bond Mechanism Z (CBM-Z) gas-phase chemical mechanism. We train the network to match CBM-Z predictions of changes in concentrations of 77 chemical species after one hour, given a range of chemical and meteorological input conditions, which it is able to do with root-mean-square error (RMSE) of less than 1.97 ppb (median RMSE = 0.02 ppb), while achieving a 250x computational speedup. An additional 17x speedup (total 4250x speedup) is achieved by running the neural network on a graphics-processing unit (GPU). The neural network is able to reproduce the emergent behavior of the chemical system over diurnal cycles using Euler integration, but additional work is needed to constrain the propagation of errors as simulation time progresses.

PYSCF is a Python-based general-purpose electronic structure platform that both supports first-principles simulations of molecules and solids, as well as accelerates the development of new methodology and complex computational workflows. The present paper explains the design and philosophy behind PYSCF that enables it to meet these twin objectives. With several case studies, we show how users can easily implement their own methods using PYSCF as a development environment. We then summarize the capabilities of PYSCF for molecular and solid-state simulations. Finally, we describe the growing ecosystem of projects that use PYSCF across the domains of quantum chemistry, materials science, machine learning and quantum information science.

Graph neural networks have recently achieved great successes in predicting quantum mechanical properties of molecules. These models represent a molecule as a graph using only the distance between atoms (nodes). They do not, however, consider the spatial direction from one atom to another, despite directional information playing a central role in empirical potentials for molecules, e.g. in angular potentials. To alleviate this limitation we propose directional message passing, in which we embed the messages passed between atoms instead of the atoms themselves. Each message is associated with a direction in coordinate space. These directional message embeddings are rotationally equivariant since the associated directions rotate with the molecule. We propose a message passing scheme analogous to belief propagation, which uses the directional information by transforming messages based on the angle between them. Additionally, we use spherical Bessel functions and spherical harmonics to construct theoretically well-founded, orthogonal representations that achieve better performance than the currently prevalent Gaussian radial basis representations while using fewer than 1/4 of the parameters. We leverage these innovations to construct the directional message passing neural network (DimeNet). DimeNet outperforms previous GNNs on average by 76% on MD17 and by 31% on QM9. Our implementation is available online.

The rapid advancements in artificial intelligence (AI) are catalyzing transformative changes in atomic modeling, simulation, and design. AI-driven potential energy models have demonstrated the capability to conduct large-scale, long-duration simulations with the accuracy of ab initio electronic structure methods. However, the model generation process remains a bottleneck for large-scale applications. We propose a shift towards a model-centric ecosystem, wherein a large atomic model (LAM), pre-trained across multiple disciplines, can be efficiently fine-tuned and distilled for various downstream tasks, thereby establishing a new framework for molecular modeling. In this study, we introduce the DPA-2 architecture as a prototype for LAMs. Pre-trained on a diverse array of chemical and materials systems using a multi-task approach, DPA-2 demonstrates superior generalization capabilities across multiple downstream tasks compared to the traditional single-task pre-training and fine-tuning methodologies. Our approach sets the stage for the development and broad application of LAMs in molecular and materials simulation research.

High-throughput data generation methods and machine learning (ML) algorithms have given rise to a new era of computational materials science by learning relationships among composition, structure, and properties and by exploiting such relations for design. However, to build these connections, materials data must be translated into a numerical form, called a representation, that can be processed by a machine learning model. Datasets in materials science vary in format (ranging from images to spectra), size, and fidelity. Predictive models vary in scope and property of interests. Here, we review context-dependent strategies for constructing representations that enable the use of materials as inputs or outputs of machine learning models. Furthermore, we discuss how modern ML techniques can learn representations from data and transfer chemical and physical information between tasks. Finally, we outline high-impact questions that have not been fully resolved and thus, require further investigation.

For the large and chemically diverse GMTKN55 benchmark suite, we have studied the performance of density-corrected density functional theory (HF-DFT), compared to self-consistent DFT, for several pure and hybrid GGA and meta-GGA exchange-correlation (XC) functionals (PBE, BLYP, TPSS, SCAN) as a function of the percentage of HF exchange in the hybrid. The D4 empirical dispersion correction has been added throughout. For subsets dominated by dynamical correlation -- particularly noncovalent interaction subsets -- HF-DFT is highly beneficial, particularly at low HF exchange percentages. For subsets with significant static correlation (i.e., where a Hartree-Fock determinant is not a good zero-order wavefunction), HF-DFT may do more harm than good. While the self-consistent series show optima at or near 37.5% (i.e., 3/8) for all four XC functionals -- consistent with Grimme's proposal of the PBE38 functional -- HF-BnLYP-D4, HF-PBEn-D4, and HF-TPSSn-D4 all exhibit minima nearer 25% (i.e., 1/4). Intriguingly, for HF-SCANn-D4, the minimum is near 10%, but the weighted mean absolute error (WTMAD2) for GMTKN55 is only barely lower than that of HF-SCAN-D4 (i.e., where the post-HF step is a pure meta-GGA). The latter becomes an attractive option, only slightly more costly than pure Hartree-Fock, and devoid of adjustable parameters other than the three in the dispersion correction. Moreover, its WTMAD2 is only surpassed by the highly empirical M06-2X and by the combinatorically optimized empirical range-separated hybrids wB97X-V and wB97M-V.

Machine learning-based interatomic potentials and force fields depend critically on accurate atomic structures, yet such data are scarce due to the limited availability of experimentally resolved crystals. Although atomic-resolution electron microscopy offers a potential source of structural data, converting these images into simulation-ready formats remains labor-intensive and error-prone, creating a bottleneck for model training and validation. We introduce AutoMat, an end-to-end, agent-assisted pipeline that automatically transforms scanning transmission electron microscopy (STEM) images into atomic crystal structures and predicts their physical properties. AutoMat combines pattern-adaptive denoising, physics-guided template retrieval, symmetry-aware atomic reconstruction, fast relaxation and property prediction via MatterSim, and coordinated orchestration across all stages. We propose the first dedicated STEM2Mat-Bench for this task and evaluate performance using lattice RMSD, formation energy MAE, and structure-matching success rate. By orchestrating external tool calls, AutoMat enables a text-only LLM to outperform vision-language models in this domain, achieving closed-loop reasoning throughout the pipeline. In large-scale experiments over 450 structure samples, AutoMat substantially outperforms existing multimodal large language models and tools. These results validate both AutoMat and STEM2Mat-Bench, marking a key step toward bridging microscopy and atomistic simulation in materials science.The code and dataset are publicly available at https://github.com/yyt-2378/AutoMat and https://huggingface.co/datasets/yaotianvector/STEM2Mat.