Automated, Accurate, and Scalable Relative Protein-Ligand Binding Free-Energy Calculations Using Lambda Dynamics.

ABSTRACT: Accurate predictions of changes to protein-ligand binding affinity in response to chemical modifications are of utility in small-molecule lead optimization. Relative free-energy perturbation (FEP) approaches are one of the most widely utilized for this goal but involve significant computational cost, thus limiting their application to small sets of compounds. Lambda dynamics, also rigorously based on the principles of statistical mechanics, provides a more efficient alternative. In this paper, we describe the development of a workflow to set up, execute, and analyze multisite lambda dynamics (MSLD) calculations run on GPUs with CHARMM implemented in BIOVIA Discovery Studio and Pipeline Pilot. The workflow establishes a framework for setting up simulation systems for exploratory screening o

SUBMITTER: Raman EP 

PROVIDER: S-EPMC7814773 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature