Importance of protein flexibility in ranking ERK2 Type I^1/2 inhibitor affinities: a computational study.

ABSTRACT: Extracellular-regulated kinase (ERK2) has been regarded as an essential target for various cancers, especially melanoma. Recently, pyrrolidine piperidine derivatives were reported as Type I^1/2 inhibitors of ERK2, which occupy both the ATP binding pocket and the allosteric pocket. Due to the dynamic behavior of ERK2 upon the binding of Type I^1/2 inhibitors, it is difficult to predict the binding structures and relative binding potencies of these inhibitors with ERK2 accurately. In this work, the binding mechanism of pyrrolidine piperidines was discussed by using different simulation techniques, including molecular docking, ensemble docking based on multiple receptor conformation, molecular dynamics simulations and free energy calculations. Our computational results sho

SUBMITTER: Niu Y 

PROVIDER: S-EPMC9063686 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature