Deciphering allosteric mechanisms in KRAS activation: insights from GTP-induced conformational dynamics and interaction network reorganization.

The conformational dynamics and activation mechanisms of KRAS proteins are of great importance for targeted cancer therapy. However, the detailed molecular mechanics of KRAS activation induced by GTP binding remains unclear. In this study, we systematically investigated how GTP/GDP exchange affects the thermodynamic and kinetic properties of KRAS and explored the activation mechanism using molecular dynamics (MD) simulations, Markov state models (MSMs), and neural relational inference (NRI) models.