Validation of an Allosteric Binding Site of Src Kinase Identified by Unbiased Ligand Binding Simulations.

ABSTRACT: Allostery plays a primary role in regulating protein activity, making it an important mechanism in human disease and drug discovery. Identifying allosteric regulatory sites to explore their biological significance and therapeutic potential is invaluable to drug discovery; however, identification remains a challenge. Allosteric sites are often "cryptic" without clear geometric or chemical features. Since allosteric regulatory sites are often less conserved in protein kinases than the orthosteric ATP binding site, allosteric ligands are commonly more specific than ATP competitive inhibitors. We present a generalizable computational protocol to predict allosteric ligand binding sites based on unbiased ligand binding simulation trajectories. We demonstrate the feasibility of this protocol by r

SUBMITTER: Mingione VR 

PROVIDER: S-EPMC9713948 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature