Kinetic and thermodynamic allostery in the Ras protein family.

ABSTRACT: Allostery, the transfer of information between distant parts of a macromolecule, is a fundamental feature of protein function and regulation. However, allosteric mechanisms are usually not explained by protein structure, requiring information on correlated fluctuations uniquely accessible to molecular simulation. Existing work to extract allosteric pathways from molecular dynamics simulations has focused on thermodynamic correlations. Here, we show how kinetic correlations encode complementary information essential to explain observed variations in allosteric regulation. We applied kinetic and thermodynamic correlation analysis on atomistic simulations of H, K, and NRas isoforms in the apo, GTP, and GDP-bound states of Ras protein, with and without complexing to its downstream effector, Ra

SUBMITTER: Manley LJ 

PROVIDER: S-EPMC10560677 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature