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

基本信息

批准号：
10202635
负责人：
LILLIAN T CHONG
金额：
$ 28.36万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10202635
关键词：
Algorithmic Software Algorithms Amber Architecture Binding Proteins Biological Biological Process Biomedical Computing Biomedical Research Budgets Capsid Cell model Cells Cloud Computing Communication Complex Computer software Computers Data Analyses Data Storage and Retrieval Development Drug Design Educational workshop Effectiveness Environment Equilibrium Event Funding Future Genes Heterogeneity Investigation Kinetics Malignant Neoplasms Manuals Maps Modeling Molecular Multiprotein Complexes Pathologic Pathway interactions Performance Pharmaceutical Preparations Phenotype Phosphorylation Physiological Process Proteins Research Research Personnel Running Sampling Series Signal Transduction Silicon Statistical Computing System Time Training Uncertainty Viral Virus base cell behavior combinatorial conformational conversion cost design improved innovation insight interoperability knowledge base molecular dynamics molecular scale open source parallelization particle protein complex protein folding residence simulation simulation software single-cell RNA sequencing tool usability

项目摘要

High-performance weighted ensemble software for simulation of complex bio-events (Renewal) 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. The WESTPA software package is a powerful “meta tool” which can make possible computations which otherwise would be impossible within a given computing budget - while letting researchers continue to use simulation engines and models of their choice. WESTPA controls existing dynamics engines by orchestrating up to thousands of trajectories run natively by those packages at any scale (e.g., Gromacs, Amber, BioNetGen, MCell) using a “weighted ensemble” strategy. Not only does WESTPA automatically 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 and equilibrium observables in significantly less computing time than would be required in ordinary parallelization. The aims of the proposal are (i) to optimize WESTPA for cloud-computing, improving its ease of use, and developing highly scalable data storage analysis; (ii) to expand WESTPA’s base-computing power via algorithmic improvements; and (iii) to demonstrate the effectiveness of WESTPA through a series of “showcase” examples from molecular to cellular scale using a variety of dynamics engines. Completion of the aims will enable the investigators, their experimental and computational collaborators, and users throughout the world to make a wide range of contributions to the burgeoning field of biological simulation at multiple scales.

用于模拟复杂生物事件的高性能加权集成软件（更新）存在一个“硅天花板”，最终限制了许多（如果不是大多数）类型的动态生物也就是说，即使是世界上最强大的计算机也无法生成足够长的时间。模拟，无论是蛋白质的原子模型还是细胞行为的现实模型。在这种情况下，关键事件可能会超出模拟时间尺度发生——例如蛋白质折叠、蛋白质的构象转变、蛋白质复合物的组装或细胞行为的转变 WESTPA 软件包是一个强大的“元工具”，可以从健康状态到病理状态。使在给定的计算预算内不可能进行的计算成为可能 - 同时让研究人员继续使用他们选择的模拟引擎和模型。现有的控制动态引擎通过编排多达数千个本地运行的轨迹使用“加权集成”的任何规模的软件包（例如 Gromacs、Amber、BioNetGen、MCell） WESTPA 不仅自动并行使用动态引擎，而且还因为。通过添加和删除轨迹的统计过程，WESTPA 可以获得估计值关键动力学和平衡可观测值的计算时间明显少于所需的计算时间该提案的目标是 (i) 优化 WESTPA 的云计算，提高其易用性，并开发高度可扩展的数据存储分析； WESTPA 通过算法改进的基础计算能力；以及 (iii) 展示通过一系列从分子到细胞尺度的“展示”示例来展示 WESTPA 的有效性使用各种动力学引擎来完成目标将使研究人员及其他们的研究人员能够实现目标。实验和计算合作者以及世界各地的用户做出了广泛的对多尺度生物模拟新兴领域的贡献。