CHARMM Modernization, Performance, and Continued Development

CHARMM（哈佛大学大分子力学化学系）是二十多年来生物学中大分子模拟和建模的主要研究工具。在此期间，CHARMM的发展及其应用定义了生物分子计算领域。该提案旨在通过解决软件组件及其伴随的支持基础设施在开发、性能和维护方面的瓶颈，确保CHARMM将继续作为未来几代科学家的开发平台。具体来说，重构代码将为CHARMM中的底层计算内核提供改进，这将显著提高单处理器性能并改善并行扩展。重点将放在提高两个目标系统尺寸的并行性上。对于代表许多“典型”应用的50-200K原子系统，我们将开发、调整和部署能够在“部门可访问”并行平台（约100个具有高带宽互连的商品处理器）上实现分子动力学紧密耦合并行的良好并行效率（大于70%）的方法。对于大型“超级计算机”上的大型生物问题，即在0.5-2K处理器上运行的接近1M原子的系统，我们将为CHARMM开发和实现新的模拟内核，利用这些系统的大空间维度，并采用空间分解和任务级并行技术。最后，我们将开发和改进代码和算法，允许基于图形处理器的加速用于CHARMM势和方法家族。这些努力的结果将是一个程序平台，将促进大分子模拟和建模的持续前沿研究，并使其能够继续发展和维护未来几代研究人员。

DESCRIPTION (provided by applicant): CHARMM (Chemistry at Harvard Macromolecular Mechanics) has been a primary research tool for macromolecular simulations and modeling in biology for over two decades. During this period CHARMM development, and applications emerging from its use, have defined the field of biomolecular computation. This proposal is aimed at ensuring CHARMM will continue as the development platform for future generations of scientists by addressing components of the software and its attendant support infrastructure that represent bottlenecks in development, performance and maintenance. Specifically, restructuring the code will provide improvements to underlying computational kernels in CHARMM, which will significantly enhance single processor performance and improve parallel scaling. Emphasis will be given to improving parallelism for two target system sizes. For systems of 50-200K atoms, which represent many "typical" applications, we will develop, adapt and deploy methods that yield good parallel efficiency (greater than 70%) for tightly coupled parallelism in molecular dynamics on "department accessible" parallel platforms (~100 commodity processors with a high bandwidth interconnect). For large biological problems on large "supercomputers", i.e. for systems approaching 1M atoms running on 0.5-2K processors, we will develop and implement new simulation kernels for CHARMM that exploit the large spatial dimensions of these systems and employ techniques of spatial decomposition and task-level parallelism. Finally, we will develop and improve code and algorithms allowing graphics processor based acceleration to be utilized for the family of CHARMM potentials and methods. The outcome of these efforts will be a program platform that will facilitate continued forefront research in macromolecular simulation and modeling and enable its continued development and maintenance for future generations of researchers. PUBLIC HEALTH RELEVANCE: CHARMM (Chemistry at Harvard Macromolecular Mechanics) has been a primary research tool for macromolecular simulations and modeling in biology for over two decades, assisting biomedical researchers in theoretical investigations of protein/nucleic acid-ligand interactions, enzyme mechanism, protein/nucleic acid folding, free energy and docking simulations for drug discovery and design, and a large range of other applications in protein, nucleic acid and membrane modeling. The nearly 14,000 citations to CHARMM attests to the pivotal role this software package has in the biomedical community. The aims of this proposal are to continue to modernize, improve performance, and secure a solid pathway for continued development of the CHARMM package to ensure its ongoing availability for biomedical researchers.