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OPLS3e: Extending Force Field Coverage for Drug-Like Small Molecules

Journal of Chemical Theory and Computation · 2019 · Vol. 15(3) · pp. 1863–1874

Katarina Roos(Uppsala University)Chuanjie Wu(Schrodinger (United States))Wolfgang Damm(Schrodinger (United States))Mark Reboul(Schrodinger (United States))James Stevenson(Schrodinger (United States))Chao Lü(Schrodinger (United States))Markus K. Dahlgren(Schrodinger (United States))Sayan Mondal(Schrodinger (United States))Wei Chen(Schrodinger (United States))Lingle Wang(Schrodinger (United States))Robert Abel(Schrodinger (United States))Richard A. Friesner(Columbia University)Edward Harder✉(Schrodinger (United States))

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Abstract

Building upon the OPLS3 force field we report on an enhanced model, OPLS3e, that further extends its coverage of medicinally relevant chemical space by addressing limitations in chemotype transferability. OPLS3e accomplishes this by incorporating new parameter types that recognize moieties with greater chemical specificity and integrating an on-the-fly parametrization approach to the assignment of partial charges. As a consequence, OPLS3e leads to greater accuracy against performance benchmarks that assess small molecule conformational propensities, solvation, and protein-ligand binding.

Protein Structure and Dynamics Enzyme Structure and Function ATP Synthase and ATPases ResearchForce field (fiction)Computer scienceField (mathematics)DrugNanotechnologyData scienceMaterials scienceMedicinePharmacologyArtificial intelligence

MeSH terms

HumansLigandsMolecular ConformationProtein BindingProteinsQuantum TheoryThermodynamicsAspartic Acid EndopeptidasesAmyloid Precursor Protein SecretasesSmall Molecule LibrariesMolecular Dynamics SimulationMolecular Docking Simulation