Collaborative Assessment of Molecular Geometries and Energies from the Open Force Field

D’Amore, Lorenzo and Hahn, David F. and Dotson, David L. and Horton, Joshua T. and Anwar, Jamshed and Craig, Ian and Fox, Thomas and Gobbi, Alberto and Lakkaraju, Sirish Kaushik and Lucas, Xavier and Meier, Katharina and Mobley, David L. and Narayanan, Arjun and Schindler, Christina E. M. and Swope, William C. and in ’t Veld, Pieter J. and Wagner, Jeffrey and Xue, Bai and Tresadern, Gary (2022) Collaborative Assessment of Molecular Geometries and Energies from the Open Force Field. Journal of Chemical Information and Modeling, 62 (23). pp. 6094-6104. ISSN 1549-9596

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Abstract

Force fields form the basis for classical molecular simulations, and their accuracy is crucial for the quality of, for instance, protein-ligand binding simulations in drug discovery. The huge diversity of small-molecule chemistry makes it a challenge to build and parameterize a suitable force field. The Open Force Field Initiative is a combined industry and academic consortium developing a state-of-the-art small-molecule force field. In this report, industry members of the consortium worked together to objectively evaluate the performance of the force fields (referred to here as OpenFF) produced by the initiative on a combined public and proprietary dataset of 19,653 relevant molecules selected from their internal research and compound collections. This evaluation was important because it was completely blind; at most partners, none of the molecules or data were used in force field development or testing prior to this work. We compare the Open Force Field "Sage" version 2.0.0 and "Parsley" version 1.3.0 with GAFF-2.11-AM1BCC, OPLS4, and SMIRNOFF99Frosst. We analyzed force-field-optimized geometries and conformer energies compared to reference quantum mechanical data. We show that OPLS4 performs best, and the latest Open Force Field release shows a clear improvement compared to its predecessors. The performance of established force fields such as GAFF-2.11 was generally worse. While OpenFF researchers were involved in building the benchmarking infrastructure used in this work, benchmarking was done entirely in-house within industrial organizations and the resulting assessment is reported here. This work assesses the force field performance using separate benchmarking steps, external datasets, and involving external research groups. This effort may also be unique in terms of the number of different industrial partners involved, with 10 different companies participating in the benchmark efforts.

Item Type:
Journal Article
Journal or Publication Title:
Journal of Chemical Information and Modeling
Additional Information:
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Chemical Information and Modeling, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.jcim.2c01185
Uncontrolled Keywords:
Research Output Funding/yes_externally_funded
Subjects:
?? library and information sciencescomputer science applicationsgeneral chemical engineeringgeneral chemistryyes - externally fundedchemistry(all)chemical engineering(all)library and information sciencescomputer science applications ??
ID Code:
185466
Deposited By:
Deposited On:
31 Jan 2023 15:20
Refereed?:
Yes
Published?:
Published
Last Modified:
08 Jun 2024 00:41