Prediction of Drug-Target Binding Kinetics by Comparative Binding Energy Analysis.

ABSTRACT: A growing consensus is emerging that optimizing the drug-target affinity alone under equilibrium conditions does not necessarily translate into higher potency in vivo and that instead binding kinetic parameters should be optimized to ensure better efficacy. Therefore, in silico methods are needed to predict the kinetic parameters and the mechanistic determinants of drug-protein binding. Here we demonstrate the application of COMparative BINding Energy (COMBINE) analysis to derive quantitative structure-kinetics relationships (QSKRs) for the dissociation rate constants (k _off) of inhibitors of heat shock protein 90 (HSP90) and HIV-1 protease. We derived protein-specific scoring functions by correlating k _off rate constants with a subset of weighted intera

SUBMITTER: Ganotra GK 

PROVIDER: S-EPMC6231175 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature