The Computational Microscope

计算显微镜

• 批准号: 1440026
• 负责人: Emad Tajkhorshid
• 金额: $ 4万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1440026&HistoricalAwards=false
• 关键词: Computational; Microscope

Cells are the building blocks of life, yet they are themselves acollection of proteins, small molecules, and solvent, none of whichare, in and of themselves, alive. How living things can arise from the"behavior" of molecules, which are simply obeying the laws of physics,is the essential conundrum of modern biology. The rise of scientificsupercomputing has offered the chance to study living systems at thelevels of atoms, cells, and all levels in between.  With Blue Waters,it is now possible to take the most critical step from inanimate toanimate matter by describing assembly and cooperation of thousands ofmacromolecules made of billions of atoms.  The ability to exploreliving systems via the "computational microscope" of moleculardynamics simulations has a profound impact not only on the progress ofbasic science, but also in the treatment of disease and thedevelopment of drugs.This project will use Blue Waters to study three types of biomolecularsystems: the microtubules that make up the cell's cytoskeleton, thechemosensory array that acts as a "bacterial brain", and two highlyrelevant retroviruses: HIV (human immunodeficiency virus) and RSV(Rous sarcoma virus).  The first project will model microtubules, intheir native form, as well as the interactions between themicrotubule, its regulatory partners, and anti-cancer agents.Simulations of the microtubule and its interactions with drugs canhelp drive the development of new microtubule-attacking cancertherapies.  The HIV part of the virus project builds on prior successin modeling the full HIV capsid to evaluate the effects of HIV drugson capsid stability and to model the essential interactions betweenthe capsid and host cell factors. Simulations of the HIV capsidprovide the necessary detailed knowledge of the vital infectionprocess to develop new HIV therapies.  The RSV part of the virusproject has constructed the first model of an intermediate stage invirus capsid maturation, which will be used to describe the maturationprocess of retroviruses may open the doors to a new type of anti-viraldrug which attacks that maturation process.  The chemosensory arrayproject seeks to answer how input from many chemical sensors on thebacterial surface are transduced across hundreds of nanometers in thearray, leading the cell to decide if it should continue swimming orchange direction, to adapt to changing environments.  The chemosensoryarray is a universal structure in bacteria, but absent in eukaryotes,offering a new target for antibiotic drugs - a desperately neededadvancement in combating bacterial resistance to current antibiotics.Each of the projects proposed presents an opportunity for petascalecomputing to contribute to mankind?s health and to answer one ofmankind's oldest questions: "What is life?"

细胞是生命的基石，但它们本身是蛋白质、小分子和溶剂的集合体，其中没有一个是活的。生物是如何从分子的“行为”中产生的，分子只是服从物理定律，这是现代生物学的基本难题。科学超级计算的兴起提供了在原子、细胞和其间所有层次上研究生命系统的机会。有了蓝色沃茨，通过描述由数十亿个原子组成的数千个大分子的组装和合作，现在可以迈出从无生命物质到有生命物质的最关键的一步。分子动力学模拟技术不仅对基础科学的进步，而且对疾病的治疗和药物的开发都有着深远的影响。本项目将利用Blue沃茨研究三种类型的生物分子系统：构成细胞骨架的微管，充当“细菌大脑”的化学传感器阵列，以及两种高度相关的逆转录病毒：艾滋病毒（人类免疫缺陷病毒）和RSV（劳斯肉瘤病毒）。第一个项目将模拟微管，在他们的天然形式，以及微管之间的相互作用，其监管伙伴，微管及其与药物相互作用的模拟可以帮助推动新微管的开发，病毒项目的HIV部分建立在先前成功建立完整的HIV衣壳模型的基础上，以评估HIV药物对衣壳稳定性的影响，并建立衣壳和宿主细胞因子HIV衣壳的模拟为开发新的HIV治疗方法提供了重要感染过程的必要详细知识。病毒项目的RSV部分构建了病毒衣壳成熟中间阶段的第一个模型，这将被用来描述逆转录病毒的成熟过程，可能会打开一扇大门，一种新型的抗-化学传感器阵列项目试图回答来自细菌表面的许多化学传感器的输入是如何在阵列中的数百纳米范围内进行转导的，引导细胞决定是否应该继续游动或改变方向，以适应不断变化的环境。化学传感器阵列是细菌中的通用结构，但在真核生物中不存在，为抗生素药物提供了一个新的靶点在对抗细菌对当前抗生素的耐药性方面，这是一个迫切需要的进步。提出的每一个项目都提供了一个机会，千万亿次计算为人类做贡献？并回答人类最古老的问题之一：“生命是什么？"