Simulating vesicle fusion on Blue Waters

该奖项授予斯坦福大学，以促进科学研究使用名为Blue Waters的大型新计算资源，该资源计划部署在伊利诺伊大学厄巴纳-香槟分校。PI将研究膜融合，即神经元胞外分泌和被包膜病毒感染发生的过程。众所周知，这种机制很难在分子水平上进行表征。部分问题在于融合蛋白催化的潜在反应尚不完全清楚。对脂膜融合机制和病毒融合蛋白催化机制的强大预测模型的发展将极大地有助于理解潜在的物理过程，以及如何有效地用抗病毒药物靶向它。在Blue Waters上的模拟将使用Gromacs软件包进行。这一项目将对千兆级分子动力学模拟软件的发展、紧密耦合的超级计算机与分布式计算的集成以及我们对膜融合的理解做出重大贡献。分子动力学在其对生物分子的化学动力学和机制进行计算预测的能力方面处于开创性扩展的边缘。该项目旨在实现对生理相关的复杂系统进行此类预测的愿景。这不仅需要扩展到更大的系统，而且需要开发复杂反应的分析方法。合作团队包括GROMACS仿真软件和Folding@Home仿真分析平台的开发人员。作为该项目的一部分开发的模拟和分析方法将以改进公开可用的GROMACS软件和SimTK网站上的开源软件包的形式与科学界共享。

This award to Stanford University facilitates scientific research using the large new computational resource named Blue Waters scheduled to be deployed at the University of Illinois at Urbana-Champaign. The PI will investigate membrane fusion, the process by which neuronal exocytosis and infection by enveloped viruses occur. This mechanism has been notoriously difficult to characterize at a molecular level. Part of the problem is that the underlying reaction that fusion proteins catalyze is not fully understood. The development of robust predictive models for the mechanism of lipid membrane fusion and its catalysis by viral fusion proteins will greatly aid in the understanding of the underlying physical process and how to effectively target it with antiviral agents. Simulations on Blue Waters will be performed using the Gromacs software package.This project will contribute substantially to the development of peta-scale molecular dynamics simulation software, the integration of tightly-coupled supercomputers with distributed computing, and our understanding of membrane fusion. Molecular dynamics is poised on the edge of a seminal expansion in its capability to make computational predictions of chemical kinetics and mechanism for biomolecules. This project aims to realize the vision of making such predictions for complex systems of physiological relevance. Such entails not merely scaling to systems of larger size but developing analytic methodology for complex reactions. The collaborative team includes developers of both the GROMACS simulation software and the Folding@Home simulation and analysis platform. Simulation and analysis methodology developed as part of this project will be shared with the scientific community in the form of improvements to the publicly available GROMACS software and the open-source software packages on the SimTK website.