Molecular motion and drug discovery under a computational microscope

发布时间 :2018-12-07  阅读次数 :1961

报告人:Huafeng Xu, Ph.D., Silicon Therapeutics首席技术官

时间:12月11日,周二,下午2:00-3:00

地点:上海交通大学 生物药学楼 树华报告厅

邀请人:孙淮教授(化学化工学院),赵一雷教授(生命科学技术学院)

报告摘要:

随着计算能力的快速发展,分子模拟已成为生物物理化学研究的常用方法,在模拟计算方法和分子力场研究取得了重要进展。在制药工业领域,分子模拟作为研究蛋白质构象变化的有力工具,应用于药物理性设计,从而探索罕见的药物作用模式,如变构抑制剂或变构激动剂。这里我结合抗体亲和力成熟过程和有选择性的激酶抑制两方面工作,着重讨论分子模拟在研究蛋白质构象动力学和计算机辅助药物设计的应用。最后,我会简要提及模拟方法和分子力场开发的工作进展。

个人简介:

Huafeng Xu担任Silicon Therapeutics公司首席技术官。Silicon Therapeutics是一家应用计算技术从事创新药物研发的高科技生物公司。Huafeng Xu在北京大学获得理学学士,在哥伦比亚大学获得硕士和博士学位。Huafeng Xu博士在D. E. Shaw Research工作了12年,涉及分子模拟的软硬件开发:自由能计算以及分子动力学模拟专用Anton芯片的设计。他的研究兴趣包括模拟计算方法开发、结构免疫学、蛋白质折叠和错误折叠、以及药物设计。

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.

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