Na⁺-binding modes involved in thrombin's allosteric response as revealed by molecular dynamics simulations, correlation networks and Markov modeling.

ABSTRACT: The monovalent sodium ion (Na+) is a critical modulator of thrombin. However, the mechanism of thrombin's activation by Na+ has been widely debated for more than twenty years. Details of the linkage between thrombin and Na+ remain vague due to limited temporal and spatial resolution in experiments. In this work, we combine microsecond scale atomic-detailed molecular dynamics simulations with correlation network analyses and hidden Markov modeling to probe the detailed thermodynamic and kinetic picture of Na+-binding events and their resulting allosteric responses in thrombin. We reveal that ASP189 and ALA190 comprise a stable Na+-binding site (referred as "inner" Na+-binding site) along with the previously known one (referred as "outer" Na+-binding site). The corresponding newly identified

SUBMITTER: Xiao J 

PROVIDER: S-EPMC6993936 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature