【11th.Dec.】Molecular motion and drug discovery under a computational microscope
日期：2018-12-11
閱讀：1002
題目: Molecular motion and drug discovery under a computational microscope
報告人：Huafeng Xu, Ph.D., Silicon Therapeutics首席技術(shù)官
時間：12月11日，周二，下午2:00-3:00
地點(diǎn)：上海交通大學(xué) 生物藥學(xué)樓 樹華報告廳
邀請人：孫淮教授(化學(xué)化工學(xué)院)，趙一雷教授（生命科學(xué)技術(shù)學(xué)院）
報告摘要
? 隨著計算能力的快速發(fā)展，分子模擬已成為生物物理化學(xué)研究的常用方法，在模擬計算方法和分子力場研究取得了重要進(jìn)展。在制藥工業(yè)領(lǐng)域，分子模擬作為研究蛋白質(zhì)構(gòu)象變化的有力工具，應(yīng)用于藥物理性設(shè)計，從而探索罕見的藥物作用模式，如變構(gòu)抑制劑或變構(gòu)激動劑。這里我結(jié)合抗體親和力成熟過程和有選擇性的激酶抑制兩方面工作，著重討論分子模擬在研究蛋白質(zhì)構(gòu)象動力學(xué)和計算機(jī)輔助藥物設(shè)計的應(yīng)用。最后，我會簡要提及模擬方法和分子力場開發(fā)的工作進(jìn)展。
個人簡介
? Huafeng Xu擔(dān)任Silicon Therapeutics公司首席技術(shù)官。Silicon Therapeutics是一家應(yīng)用計算技術(shù)從事創(chuàng)新藥物研發(fā)的高科技生物公司。Huafeng Xu在北京大學(xué)獲得理學(xué)學(xué)士，在哥倫比亞大學(xué)獲得碩士和博士學(xué)位。Huafeng Xu博士在D. E. Shaw Research工作了12年，涉及分子模擬的軟硬件開發(fā)：自由能計算以及分子動力學(xué)模擬專用Anton芯片的設(shè)計。他的研究興趣包括模擬計算方法開發(fā)、結(jié)構(gòu)免疫學(xué)、蛋白質(zhì)折疊和錯誤折疊、以及藥物設(shè)計。
Abstract
Molecular simulations are now routinely used in biophysical research, thanks to three key developments in the past decade: rapid expansion of computational power enabled by graphics processing units and specialized integrated circuits, substantial advances in computational methods, and significant improvements in the accuracy of force fields. In the meantime, the pharmaceutical industry, challenged by increasingly difficult targets, is exploring uncommon modes of drug actions, such as allosteric inhibitors and agonists. Molecular simulations can play an instrumental role in the rational design of such conformational modulators of proteins. I will discuss the application of molecular simulations in the study of protein conformational dynamics and in computer-aided drug discovery, with case studies in antibody affinity maturation, selective kinase inhibition, and allosteric inhibition of phosphatases. I will also outline our on-going work in method and force field development, in an effort to build a better computational microscope that can “observe” biomolecules at atomistic resolutions.
Biography
Huafeng Xu is the Chief Technology Officer of Silicon Therapeutics, a biotech company that uses physics-based computation to develop drugs against traditionally “undruggable” protein targets. He earned his Bachelor of Science from Peking University, and his Master and Ph. D. from Columbia University. Before joining Silicon Therapeutics, he had spent 12 years in D. E. Shaw Research, where he played an early role in the design of the specialized Anton chip for molecular dynamics simulations, and he led the development of the methods and software for free energy calculations that are now widely used in the pharmaceutical industry. His research interests include development of simulation methods, free energy calculations, structural immunology, protein folding and misfolding, and molecular design.
