Hybrid Steered Molecular Dynamics Approach to Computing Absolute Binding Free Energy of Ligand-Protein Complexes: A Brute Force Approach That Is Fast and Accurate.

ABSTRACT: Computing the free energy of binding a ligand to a protein is a difficult task of essential importance for which purpose various theoretical/computational approaches have been pursued. In this paper, we develop a hybrid steered molecular dynamics (hSMD) method capable of resolving one ligand–protein complex within a few wall-clock days with high enough accuracy to compare with the experimental data. This hSMD approach is based on the relationship between the binding affinity and the potential of mean force (PMF) in the established literature. It involves simultaneously steering n (n = 1, 2, 3, ...) centers of mass of n selected segments of the ligand using n springs of infinite stiffness. Steering the ligand from a single initial state chosen from the bound state ensemble to the correspond

SUBMITTER: Chen LY 

PROVIDER: S-EPMC4411208 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature