arXiv subjects

J. Harry Moore

Publications and source records attributed to J. Harry Moore.

4 recordsLinked to original sources

arXiv2026

DFT Accuracy on Crystal Structure Prediction with Machine Learning Interatomic Potentials

We present an evaluation of CSP-MACE-{\AA}, a machine learning interatomic potential intended to replace DFT in crystal structure prediction (CSP). We decompose the total energy into separate intramolecular and intermolecular components. For the intramolecular component, we adopt the MACE-POLAR architecture and train it on the OMol25 dataset. The intermolecular component combines three terms: an intermolecular contribution from the MACE-POLAR model, a long-range dispersion term with the functional form of the XDM correction, and a learned delta model trained to reproduce B86bPBE-XDM intermolecular energies. The learned delta model is trained on residual intermolecular targets derived from 50,000 B86bPBE-XDM calculations on molecular crystal structures. On an evaluation set composed of 19 compounds, including a salt, selected from AstraZeneca's previous CSP publications, CSP-MACE-{\AA} achieves performance comparable to PBE DFT with the Neumann-Perrin dispersion correction. On a second evaluation set composed of 28 compounds, including cocrystals and salts, collated from the seven CSP blind tests, CSP-MACE-{\AA} achieves performance close to B86bPBE-XDM DFT. In both evaluation sets, reranking with harmonic free energies substantially improves performance relative to ranking by energy alone. Across our evaluation suite, CSP-MACE-{\AA} is shown to outperform the MACE-POLAR-1 and UMA-OMC foundation models. Lastly, on a set of five compounds, CSP-MACE-{\AA} is shown to capture temperature-dependent trends in the relative stability of polymorphs through estimation of the free energy under the harmonic approximation. By running multiple orders of magnitude faster than DFT, CSP-MACE-{\AA} enables energy and free energy evaluation of far more candidate structures, providing greater confidence when derisking solid forms.

physics.chem-ph↗

arXiv2026

Computing solvation free energies of small molecules with experimental accuracy

Free energies play a central role in characterising the behaviour of chemical systems and are among the most important quantities that can be calculated by molecular dynamics simulations. Solvation free energies in various organic solvents, in particular, are well-studied physicochemical properties of drug-like molecules and are commonly used to assess and optimise the accuracy of nonbonded parameters in empirical forcefields, and also as a fast-to-compute surrogate of performance for protein-ligand binding free energy estimation. Machine learned potentials (MLPs) show great promise as more accurate alternatives to empirical forcefields, but are not readily decomposed into physically motivated functional forms, which has thus far rendered them incompatible with standard alchemical free energy methods that manipulate individual pairwise interaction terms. However, since the accuracy of free energy calculations is highly sensitive to the forcefield, this is a key area in which MLPs have the potential to address the shortcomings of empirical forcefields. In this work, we introduce an efficient alchemical free energy protocol that enables calculations of rigorous free energy differences in condensed phase systems modelled entirely by MLPs. Using a pretrained, transferrable, alchemically equipped MLP model, we demonstrate sub-chemical accuracy for the solvation free energies of a wide range of organic molecules.

physics.chem-ph↗

arXiv2025

A foundation model for atomistic materials chemistry

Atomistic simulations of matter, especially those that leverage first-principles (ab initio) electronic structure theory, provide a microscopic view of the world, underpinning much of our understanding of chemistry and materials science. Over the last decade or so, machine-learned force fields have transformed atomistic modeling by enabling simulations of ab initio quality over unprecedented time and length scales. However, early ML force fields have largely been limited by: (i) the substantial computational and human effort of developing and validating potentials for each particular system of interest; and (ii) a general lack of transferability from one chemical system to the next. Here we show that it is possible to create a general-purpose atomistic ML model, trained on a public dataset of moderate size, that is capable of running stable molecular dynamics for a wide range of molecules and materials. We demonstrate the power of the MACE-MP-0 model - and its qualitative and at times quantitative accuracy - on a diverse set of problems in the physical sciences, including properties of solids, liquids, gases, chemical reactions, interfaces and even the dynamics of a small protein. The model can be applied out of the box as a starting or "foundation" model for any atomistic system of interest and, when desired, can be fine-tuned on just a handful of application-specific data points to reach ab initio accuracy. Establishing that a stable force-field model can cover almost all materials changes atomistic modeling in a fundamental way: experienced users get reliable results much faster, and beginners face a lower barrier to entry. Foundation models thus represent a step towards democratising the revolution in atomic-scale modeling that has been brought about by ML force fields.

physics.chem-ph↗

arXiv2025

MACE-OFF: Transferable Short Range Machine Learning Force Fields for Organic Molecules

Classical empirical force fields have dominated biomolecular simulation for over 50 years. Although widely used in drug discovery, crystal structure prediction, and biomolecular dynamics, they generally lack the accuracy and transferability required for first-principles predictive modeling. In this paper, we introduce MACE-OFF, a series of short range transferable force fields for organic molecules created using state-of-the-art machine learning technology and first-principles reference data computed with a high level of quantum mechanical theory. MACE-OFF demonstrates the remarkable capabilities of short range models by accurately predicting a wide variety of gas and condensed phase properties of molecular systems. It produces accurate, easy-to-converge dihedral torsion scans of unseen molecules, as well as reliable descriptions of molecular crystals and liquids, including quantum nuclear effects. We further demonstrate the capabilities of MACE-OFF by determining free energy surfaces in explicit solvent, as well as the folding dynamics of peptides.Finally, we simulate a fully solvated small protein, observing accurate secondary structure and vibrational spectrum. These developments enable first-principles simulations of molecular systems for the broader chemistry community at high accuracy and relatively low computational cost.

physics.chem-ph↗