Electrostatic Basis of Biological Actions

Arieh Warshel

University of Southern California
The Chinese University of Hongkong, Shenzhen

 

In this lecture, Nobel Laureate Arieh Warshel presents a monumental synthesis of over forty years of pioneering exploration. He introduces the microscopic basis of electrostatic theory and the ways to evaluate electrostatic energies in macromolecules. He rigorously develops the theoretical framework of electrostatics, introducing a hierarchy of models from all-atom representations to continuum approximations, critically evaluating their assumptions and limitations.

 

A major focus is placed on the electrostatic underpinnings of enzymatic catalysis, protein-ligand interactions, redox processes, and the folding and stability of proteins. The lecture also addresses specialized topics such as pKa calculations, ion and proton channels, and the dielectric behavior of proteins. Furthermore, the lecture examines the electrostatic basis of molecular machines, signaling mechanisms (including G-proteins and Ras), GPCR activation, and cell-cell interactions.

By integrating detailed theoretical models with biological function, Warshel provides a unifying perspective that reshapes our understanding of biomolecular action. This work serves as both a definitive reference and a forward-looking framework, emphasizing the predictive power of physically consistent electrostatic models in elucidating life at the molecular level.

 

阿里耶·瓦谢尔教授，2013年诺贝尔化学奖获得者，美国国家科学院院士，英国皇家化学会会士，现任美国南加州大学化学与生化学系杰出教授。2017年起，任香港中文大学（深圳）计算生物研究院主任。

瓦谢尔教授在生物分子功能模拟领域开创了多项关键方法，包括：将分子动力学引入生物学研究；发展量子力学/分子力学（QM/MM）方法；建立酶反应的计算模拟；率先开展溶液和蛋白质中电子转移与质子转移过程的微观模拟；开创大分子体系中静电作用的微观建模；并引入蛋白质折叠的计算模拟。已经广泛应用于不同领域；阐明了分子机器的矢量行动的分子源头。他最著名的成果是开发“多尺度分子模拟”方法并成功应用于生物分子系统以及蛋白质反应机制科研上。也借此重大发明获颁2013年诺贝尔化学奖