Collaborative Research: A Petaflop Cyberinfrastructure for Computing Free Energy Landscapes of Macro- and Biomolecular Systems

这项研究的目标是开发一个千万亿级的网络基础设施，用于有效地计算复杂的大分子和生物分子系统的自由能景观。该方法是开发一个用于在Petaflop结构上执行Wang-Landau自由能分布计算的网络基础设施，并将其应用于两个突出的科学问题(连接蛋白在溶液中的构象和脂类的自组装)。自由能是对考虑了熵和热效应的系统的能量的测量。了解包括蛋白质在内的各种大分子和生物分子的各种构象的相对自由能和相互之间的势垒，以及无序结构和自组装结构之间的相变，是化学、生物化学和生物物理学的一个极其重要的领域，也是一个计算能力增强的领域，有望取得重大进展。这项拟议的研究的智力价值在于，它有可能导致在千万亿级结构上执行自由能计算的新算法，此外还可以对大分子和生物分子系统中的构象平衡和自组装产生见解。拟议研究的更广泛影响包括开发一个强大的开源千万亿级网络基础设施，用于执行只有通过物理、化学、生物、工程和计算机科学之间的强大协同才能实现的自由能量计算。通过参与机构开展的研究以及教育和推广计划，该项目使高中生、本科生、研究生和博士后研究人员接触到计算物理、化学和材料研究的前沿。

The objective of this research is to develop a petascale cyberinfrastructure for the efficient calculation of free energy landscapes for complex macro- and biomolecular systems. The approach is to develop a cyberinfrastructure for performing Wang-Landau calculations of free energy distributions on petaflop architectures and, to demonstrate its effectiveness, apply it to two outstanding science problems (conformations of a linker protein in solution and self-assembly of lipids). Free energy is a measure of the energy of the system that takes into account entropic and thermal effects. Understanding the relative free energies of, and barriers between, various conformations of macromolecular and biological molecules, including proteins, and of phase transitions between disordered and self-assembled structures, is an extremely important area of chemistry, biochemistry and biophysics and is an area where increased computational capabilities hold the promise of significant progress. The intellectual merit of the proposed research is that it has the potential to result in new algorithms for performing free energy calculations on petascale architectures, in addition to yielding insights into conformational equilibria and self-assembly in macro- and biomolecular systems. The broader impacts of the proposed research include the development of a robust open source petascale cyberinfrastructure for performing free energy calculations made possible only through a strong synergy between physics, chemistry, biology, engineering, and computer science. Through the research performed and educational and outreach programs at the participating institutions, the project exposes high school, undergraduate and graduate students and postdoctoral researchers to the frontiers of computational physics, chemistry and materials research.