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·瓦謝爾教授，2013年諾貝爾化學(xué)獎(jiǎng)獲得者，美國(guó)國(guó)家科學(xué)院院士，英國(guó)皇家化學(xué)會(huì)會(huì)士，現(xiàn)任美國(guó)南加州大學(xué)化學(xué)與生化學(xué)系杰出教授。2017年起，任香港中文大學(xué)（深圳）計(jì)算生物研究院主任。

瓦謝爾教授在生物分子功能模擬領(lǐng)域開創(chuàng)了多項(xiàng)關(guān)鍵方法，包括：將分子動(dòng)力學(xué)引入生物學(xué)研究；發(fā)展量子力學(xué)/分子力學(xué)（QM/MM）方法；建立酶反應(yīng)的計(jì)算模擬；率先開展溶液和蛋白質(zhì)中電子轉(zhuǎn)移與質(zhì)子轉(zhuǎn)移過程的微觀模擬；開創(chuàng)大分子體系中靜電作用的微觀建模；并引入蛋白質(zhì)折疊的計(jì)算模擬。已經(jīng)廣泛應(yīng)用于不同領(lǐng)域；闡明了分子機(jī)器的矢量行動(dòng)的分子源頭。他最著名的成果是開發(fā)“多尺度分子模擬”方法并成功應(yīng)用于生物分子系統(tǒng)以及蛋白質(zhì)反應(yīng)機(jī)制科研上。也借此重大發(fā)明獲頒2013年諾貝爾化學(xué)獎(jiǎng)