报告问题 (Title)：Implicit-Solvent Modeling of Dry-Wet Transitions for Hydrophobic Binding/Unbinding（疏水连系/解离历程干湿转变的隐式溶剂模子）

报告人 (Speaker)：周圣高 教授（上海交通大学）

报告时间 (Time)：2024年11月27日 (周三) 9:30-10:30

报告所在 (Place)：校本部 GJ303课堂

约请人(Inviter)：涂一辉

主理部分：理学院数学系

报告摘要：

Solvent fluctuations play a fundamental role in many water-mediated biological processes of importance. Capillary evaporation and condensation, induced by solvent fluctuations, take place in hydrophobic confinements. Based on a variational implicit solvent model, we combine the level-set method and the string method to study such dry-wet transitions, e.g., transition pathways and energy barriers. The resulting transition rates are then used in a spatially dependent multistate Brownian dynamics simulation and the related Fokker–Planck equation calculations of a ligand–receptor system. We find the hydration transitions to significantly slow down the binding process, in semiquantitative agreement with existing explicit-water simulations, but significantly accelerate the unbinding process. Moreover, our approach allows the characterization of nonequilibrium hydration states of pocket and ligand during the ligand movement, for which we find substantial memory and hysteresis effects for binding vs. unbinding. Our study thus provides a significant step forward toward efficient, physics-based interpretation and predictions of the complex kinetics in realistic ligand–receptor systems.This is a joint work with Dr. R. G. Wei?, L. Cheng, J. Dzubiella, J. A. McCammon, and B. Li.