Sodium-induced population shift drives activation of thrombin.

ABSTRACT: The equilibrium between active E and inactive E* forms of thrombin is assumed to be governed by the allosteric binding of a Na⁺ ion. Here we use molecular dynamics simulations and Markov state models to sample transitions between active and inactive states. With these calculations we are able to compare thermodynamic and kinetic properties depending on the presence of Na⁺. For the first time, we directly observe sodium-induced conformational changes in long-timescale computer simulations. Thereby, we are able to explain the resulting change in activity. We observe a stabilization of the active form in presence of Na⁺ and a shift towards the inactive form in Na⁺-free simulations. We identify key structural features to quantify and monitor this con

SUBMITTER: Kahler U 

PROVIDER: S-EPMC6978324 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature