Development and Benchmarking of Open Force Field 2.0.0: The Sage Small Molecule Force Field.

Autor:	Boothroyd S; Boothroyd Scientific Consulting Ltd., London WC2H 9JQ, U.K., Behara PK; Department of Pharmaceutical Sciences, University of California, Irvine, California 92697, United States., Madin OC; Chemical & Biological Engineering Department, University of Colorado Boulder, Boulder, Colorado 80309, United States., Hahn DF; Computational Chemistry, Janssen Research & Development, Turnhoutseweg 30, Beerse B-2340, Belgium., Jang H; Chemistry Department, The University of California at Davis, Davis, California 95616, United States.; OpenEye Scientific Software, Santa Fe, New Mexico 87508, United States., Gapsys V; Computational Chemistry, Janssen Research & Development, Turnhoutseweg 30, Beerse B-2340, Belgium.; Computational Biomolecular Dynamics Group, Department of Theoretical and Computational Biophysics, Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, D-37077, Göttingen, Germany., Wagner JR; Department of Pharmaceutical Sciences, University of California, Irvine, California 92697, United States.; The Open Force Field Initiative, Open Molecular Software Foundation, Davis, California 95616, United States., Horton JT; School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, U.K., Dotson DL; The Open Force Field Initiative, Open Molecular Software Foundation, Davis, California 95616, United States.; Datryllic LLC, Phoenix, Arizona 85003, United States., Thompson MW; Chemical & Biological Engineering Department, University of Colorado Boulder, Boulder, Colorado 80309, United States.; The Open Force Field Initiative, Open Molecular Software Foundation, Davis, California 95616, United States., Maat J; Department of Chemistry, University of California, Irvine, California 92697, United States., Gokey T; Department of Chemistry, University of California, Irvine, California 92697, United States., Wang LP; Chemistry Department, The University of California at Davis, Davis, California 95616, United States., Cole DJ; School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, U.K., Gilson MK; Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of California at San Diego, La Jolla, California 92093, United States., Chodera JD; Computational & Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States., Bayly CI; OpenEye Scientific Software, Santa Fe, New Mexico 87508, United States., Shirts MR; Chemical & Biological Engineering Department, University of Colorado Boulder, Boulder, Colorado 80309, United States., Mobley DL; Department of Pharmaceutical Sciences, University of California, Irvine, California 92697, United States.; Department of Chemistry, University of California, Irvine, California 92697, United States.
Jazyk:	angličtina
Zdroj:	Journal of chemical theory and computation [J Chem Theory Comput] 2023 Jun 13; Vol. 19 (11), pp. 3251-3275. Date of Electronic Publication: 2023 May 11.
DOI:	10.1021/acs.jctc.3c00039
Abstrakt:	We introduce the Open Force Field (OpenFF) 2.0.0 small molecule force field for drug-like molecules, code-named Sage, which builds upon our previous iteration, Parsley. OpenFF force fields are based on direct chemical perception, which generalizes easily to highly diverse sets of chemistries based on substructure queries. Like the previous OpenFF iterations, the Sage generation of OpenFF force fields was validated in protein-ligand simulations to be compatible with AMBER biopolymer force fields. In this work, we detail the methodology used to develop this force field, as well as the innovations and improvements introduced since the release of Parsley 1.0.0. One particularly significant feature of Sage is a set of improved Lennard-Jones (LJ) parameters retrained against condensed phase mixture data, the first refit of LJ parameters in the OpenFF small molecule force field line. Sage also includes valence parameters refit to a larger database of quantum chemical calculations than previous versions, as well as improvements in how this fitting is performed. Force field benchmarks show improvements in general metrics of performance against quantum chemistry reference data such as root-mean-square deviations (RMSD) of optimized conformer geometries, torsion fingerprint deviations (TFD), and improved relative conformer energetics (ΔΔ E ). We present a variety of benchmarks for these metrics against our previous force fields as well as in some cases other small molecule force fields. Sage also demonstrates improved performance in estimating physical properties, including comparison against experimental data from various thermodynamic databases for small molecule properties such as Δ H mix , ρ( x ), Δ G solv , and Δ G trans . Additionally, we benchmarked against protein-ligand binding free energies (Δ G bind ), where Sage yields results statistically similar to previous force fields. All the data is made publicly available along with complete details on how to reproduce the training results at https://github.com/openforcefield/openff-sage.
Databáze:	MEDLINE
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