Protein-Ligand Binding Free-Energy Calculations with ARROW─A Purely First-Principles Parameterized Polarizable Force Field.

ABSTRACT: Protein-ligand binding free-energy calculations using molecular dynamics (MD) simulations have emerged as a powerful tool for in silico drug design. Here, we present results obtained with the ARROW force field (FF)─a multipolar polarizable and physics-based model with all parameters fitted entirely to high-level ab initio quantum mechanical (QM) calculations. ARROW has already proven its ability to determine solvation free energy of arbitrary neutral compounds with unprecedented accuracy. The ARROW FF parameterization is now extended to include coverage of all amino acids including charged groups, allowing molecular simulations of a series of protein-ligand systems and prediction of their relative binding free energies. We ensure adequate sampling by applying a novel technique that is base

SUBMITTER: Nawrocki G 

PROVIDER: S-EPMC9753910 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature