Investigating the conformational landscape of AlphaFold2-predicted protein kinase structures.

ABSTRACT:

Summary

Protein kinases are a family of signaling proteins, crucial for maintaining cellular homeostasis. When dysregulated, kinases drive the pathogenesis of several diseases, and are thus one of the largest target categories for drug discovery. Kinase activity is tightly controlled by switching through several active and inactive conformations in their catalytic domain. Kinase inhibitors have been designed to engage kinases in specific conformational states, where each conformation presents a unique physico-chemical environment for therapeutic intervention. Thus, modeling kinases across conformations can enable the design of novel and optimally selective kinase drugs. Due to the recent success of AlphaFold2 in accurately predicting the 3D structure of proteins based on sequence,

SUBMITTER: Al-Masri C 

PROVIDER: S-EPMC10541651 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature