Exploring Dynamic Allostery in Thrombin

Thrombin is a key enzyme in blood coagulation, essential for maintaining vascular integrity and preventing excessive bleeding. Its dysregulation, however, is linked to pathological conditions such as thrombosis and cancer. Thrombin also serves as a prototypical example of dynamic allostery, undergoing conformational changes in response to diverse binding events. Utilizing molecular dynamics simulations, coupled with statistical analyses and machine learning techniques, we investigate thrombin's allosteric transitions. Specifically, we explore thrombin's switch between slow and fast conformations, its active and inactive states, the influence of Na+ binding, the impact of light chain mutations, and its interactions with various biomolecules. Additionally, we present preliminary findings on allosteric drug design targeting thrombin. Understanding these dynamic behaviors could inform the development of more effective therapeutics aimed at modulating thrombin's function.