The Computational Microscope

这项提议是临时分配将于2011年投入使用的Blue Waters计算机系统的时间，并提供差旅资金，以支持不同合作者与Blue Waters项目团队和供应商技术团队的技术协调。该项目涉及对三种细胞系统和过程的分子动力学模拟：病毒感染、细胞内膜的形态发生和光合作用生色团。这些生物过程的作用是在时间上展开的，用结晶学很难跟踪这种进化。分子动力学模拟将为这些过程的进化提供洞察力。计划中的脊髓灰质炎病毒工作涉及使用数值模拟来研究在原子水平上的变化，这些变化负责脊髓灰质炎病毒进入细胞的过程。人们认为，这将代表一类病毒的这一过程，即无包膜RNA病毒，包括甲型肝炎、普通感冒和病毒性脑膜炎等疾病的病原体。计划中的蛋白质如何形成细胞膜的研究将提供对细胞器和囊泡形成的一个重要方面的见解。光合作用方面的工作包括研究紫色细菌中的色团，这是一个涉及200多种蛋白质的系统，在能够对细胞器建模的道路上迈出了一步。这将使研究人员能够确定醌与远端蛋白质结合时的统计首选路线，以及在驱动ATP合成和细胞运输时光产生的电势是如何传播的。这项工作中使用的分子模拟代码将被广泛使用，为化学、生物化学和材料研究领域的其他研究人员提供工具。博士后研究人员和研究生将大量参与申请拨款的项目。这项工作的结果将在医学和生物工程中使用。

This proposal is for a provisional allocation of time on the Blue Waters computer system, due to become operational in 2011, and for travel funds to support technical coordination by various collaborators with the Blue Waters project team and vendor technical team.The project involves molecular dynamics simulations of three cellular systems and processes: viral infection, morphogenesis of intra-cellular membranes, and the photosynthetic chromatophore. The actions of these biological processes unfold in time and it is difficult to follow such evolution with crystallography. Molecular dynamics simulations will provide insights into the evolution of these processes.Planned work with the poliovirus involves the use of numerical simulation to study the changes at the atomic level that are responsible for the process by which a poliovirus enters a cell. It is thought that this will be representative of this process for a class of viruses, the non-enveloped RNA viruses, that include the agents of diseases such as hepatitis A, the common cold, and viral meningitis. The planned studies of how proteins shape intracellular membranes will provide insights into an important aspect of organelle and vesicle formation. The work on photosynthesis involves studies of the chromatophore in purple bacteria, a system involving over 200 proteins and a step along the route of being able to model an organelle. This will allow researchers to determine the statistically preferred routes for quinones as they couple distant proteins, and how the light-generated electrical potential spreads as it drives ATP synthesis and cellular transport.The molecular simulation codes used in this work will be made widely available, providing tools for other researchers in the chemistry, biochemistry and materials research communities. There will be substantial involvement of post-doctoral researchers and graduate students in the projects for which the allocation is requested. The results of the work should be of use in medicine and bio-engineering.