HIGH-PERFORMANCE WEIGHTED ENSEMBLE SOFTWARE FOR SIMULATION OF COMPLEX BIO-EVENTS

用于模拟复杂生物事件的高性能加权集成软件

• 批准号: 9268876
• 负责人: LILLIAN T CHONG
• 金额: $ 6.5万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9268876
• 关键词: Amber; Benchmarking; Big Data; Binding; Bioinformatics; Biological; Biomedical Computing; Biomedical Research; Capsid; Categories; Chemicals; Communication; Complex; Computational Biology; Computer software; Computers; Custom; Data Science; Development; Documentation; Drug Design; Effectiveness; Equilibrium; Event; Exhibits; Health; Individual; Informatics; Kinetics; Lead; Length; Modeling; Molecular; Outcome; Performance; Process; Proteins; Protocols documentation; Research; Research Personnel; Running; Sampling; Series; Silicon; Software Tools; Statistical Computing; Stress Tests; System; Technology; Testing; Time; United States National Institutes of Health; Virus; Weight; base; cell behavior; chemical kinetics; computing resources; conformational conversion; data sharing; design; experience; improved; insight; interest; interoperability; learning materials; malignant neurologic neoplasms; millisecond; open source; parallelization; programs; protein complex; protein folding; response; simulation; simulation software; tool

 DESCRIPTION (provided by applicant): There is a "silicon ceiling" that ultimately limits many, if not most, types of dynamical biological simulations. That is, even the world's most powerful computers cannot generate sufficiently long simulations, whether for atomistic models of proteins or for realistic models of cell behavior. In many cases, the key events may occur beyond simulation timescales - such as protein folding, conformational transitions of proteins, assembly of protein complexes, or transitions of cell behavior from healthy to pathological states. We therefore propose a response to PA-14-156, "Extended Development, Hardening and Dissemination of Technologies in Biomedical Computing, Informatics and Big Data Science (RO1)," in which we will continue to enhance the "WESTPA" software package. WESTPA is a tool for controlling other software tools: it orchestrates up to thousands of trajectories run natively by other software at any scale (e.g., Gromacs, Amber, BioNetGen, MCell) using a "weighted ensemble" strategy. Not only does WESTPA parallelize the use of dynamics engines - but because of the statistical process by which trajectories are added and removed, WESTPA can obtain estimates of key kinetic as well as equilibrium observables in significantly less computing time than would be required in ordinary parallelization. The aims of the proposal are to improve the ease of use and interoperability of WESTPA; to improve its performance and reliability; to demonstrate the effectiveness of WESTPA through a series of "showcase" examples from molecular to cellular scale using a variety of dynamics engines; and to improve instructional materials based on the showcase examples.

 描述(申请人提供)：有一个“硅天花板”，它最终限制了许多，如果不是大多数类型的动态生物模拟。也就是说，即使是世界上最强大的计算机也不能产生足够长的模拟，无论是对蛋白质的原子模型还是对细胞行为的真实模型。在许多情况下，关键事件可能发生在模拟时间尺度之外--例如蛋白质折叠、蛋白质构象转变、蛋白质复合体的组装或细胞行为从健康状态到病理状态的转变。因此，我们建议对PA-14-156“生物医学计算、信息学和大数据科学(RO1)技术的扩展发展、强化和传播”作出回应，其中我们将继续增强“WESTPA”软件包。WESTPA是一个用于控制其他软件工具的工具：它使用“加权集成”策略编排由任何规模的其他软件(例如Gromacs、Amber、BioNetGen、Mcell)原生运行的多达数千条轨迹。WESTPA不仅使动力学引擎的使用并行化，而且由于轨迹的添加和删除的统计过程，WESTPA可以获得关键动力学和平衡观察值的估计，计算时间比普通并行化所需的计算时间要少得多。该提案的目的是改善WESTPA的易用性和互操作性；改进其性能和可靠性；通过使用各种动力学引擎从分子到细胞的一系列“展示”例子来展示WESTPA的有效性；并在展示例子的基础上改进教学材料。