Ligand Binding Thermodynamic Cycles: Hysteresis, the Locally Weighted Histogram Analysis Method, and the Overlapping States Matrix.

ABSTRACT: Free energy perturbation (FEP) simulations have been widely applied to obtain predictions of the relative binding free energy for a series of congeneric ligands binding to the same receptor, which is an essential component for the lead optimization process in computer-aided drug discovery. In the case of several congeneric ligands forming a perturbation map involving a closed thermodynamic cycle, the summation of the estimated free energy change along each edge in the cycle using Bennett acceptance ratio (BAR) usually will deviate from zero due to systematic and random errors, which is the hysteresis of cycle closure. In this work, the advanced reweighting techniques binless weighted histogram analysis method (UWHAM) and locally weighted histogram analysis method (LWHAM) are applied to pro

SUBMITTER: Cui D 

PROVIDER: S-EPMC7137390 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature