The Computational Microscope

这一提议是为了在2011年投入使用的Blue Waters计算机系统上临时分配时间，以及为支持Blue Waters项目团队和供应商技术团队的各种合作者进行技术协调提供旅费。该项目涉及三个细胞系统和过程的分子动力学模拟：病毒感染、细胞膜形态发生和光合色素。这些生物过程的作用是随时间展开的，用晶体学很难跟踪这种进化。分子动力学模拟将提供深入了解这些过程的演变。计划中的脊髓灰质炎病毒工作包括使用数值模拟来研究导致脊髓灰质炎病毒进入细胞过程的原子水平变化。据认为，这将代表一类病毒的这一过程，非包膜RNA病毒，包括疾病的病原体，如甲型肝炎、普通感冒和病毒性脑膜炎。蛋白质如何形成细胞膜的计划研究将提供细胞器和囊泡形成的一个重要方面的见解。光合作用的研究包括对紫色细菌中染色质的研究，这是一个涉及200多种蛋白质的系统，也是能够模拟细胞器的一步。这将使研究人员能够确定统计学上醌类与远距离蛋白质结合的首选路线，以及光产生的电势在驱动ATP合成和细胞运输时是如何传播的。在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界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。研究结果对医学和生物工程具有一定的应用价值。

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.