Predicting allosteric sites using fast conformational sampling as guided by coarse-grained normal modes.

ABSTRACT: To computationally identify cryptic binding sites for allosteric modulators, we have developed a fast and simple conformational sampling scheme guided by coarse-grained normal modes solved from the elastic network models followed by atomistic backbone and sidechain reconstruction. Despite the complexity of conformational changes associated with ligand binding, we previously showed that simply sampling along each of the lowest 30 modes can adequately restructure cryptic sites so they are detectable by pocket finding programs like Concavity. Here, we applied this method to study four classical examples of allosteric regulation (GluR2 receptor, GroEL chaperonin, GPCR, and myosin). Our method along with alternative methods has been utilized to locate known allosteric sites and predict new prom

SUBMITTER: Zheng W 

PROVIDER: S-EPMC10066797 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature