Toward High-Throughput Predictive Modeling of Protein Binding/Unbinding Kinetics.

ABSTRACT: One of the unaddressed challenges in drug discovery is that drug potency determined in vitro is not a reliable indicator of drug activity in vivo. Accumulated evidence suggests that in vivo activity is more strongly correlated with the binding/unbinding kinetics than the equilibrium thermodynamics of protein-ligand interactions (PLIs). However, existing experimental and computational techniques are insufficient in studying the molecular details of kinetics processes of PLIs on a large scale. Consequently, we not only have limited mechanistic understanding of the kinetic processes but also lack a practical platform for high-throughput screening and optimization of drug leads on the basis of their kinetic properties. For the first time, we address this unmet need by integrating coarse-graine

SUBMITTER: Chiu SH 

PROVIDER: S-EPMC5537004 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature