Force Field Optimization Guided by Small Molecule Crystal Lattice Data Enables Consistent Sub-Angstrom Protein-Ligand Docking.

ABSTRACT: Accurate and rapid calculation of protein-small molecule interaction free energies is critical for computational drug discovery. Because of the large chemical space spanned by drug-like molecules, classical force fields contain thousands of parameters describing atom-pair distance and torsional preferences; each parameter is typically optimized independently on simple representative molecules. Here, we describe a new approach in which small molecule force field parameters are jointly optimized guided by the rich source of information contained within thousands of available small molecule crystal structures. We optimize parameters by requiring that the experimentally determined molecular lattice arrangements have lower energy than all alternative lattice arrangements. Thousands of independe

SUBMITTER: Park H 

PROVIDER: S-EPMC8218654 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature