Potential Mean Force from Umbrella Sampling Simulations: What Can We Learn and What Is Missed?

ABSTRACT: Changes in free energy provide valuable information for molecular recognition, including both ligand-receptor binding thermodynamics and kinetics. Umbrella sampling (US), a widely used free energy calculation method, has long been used to explore the dissociation process of ligand-receptor systems and compute binding free energy. In existing publications, the binding free energy computed from the potential of mean force (PMF) with US simulation mostly yielded "ball park" values with experimental data. However, the computed PMF values are highly influenced by factors such as initial conformations and/or trajectories provided, the reaction coordinate, and sampling of conformational space in each US window. These critical factors have rarely been carefully studied. Here we used US to study th

SUBMITTER: You W 

PROVIDER: S-EPMC6456367 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature