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（更新） 有一个“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 仿真。也就是说，即使是世界上最强大的计算机也无法产生足够长的时间。 模拟，无论是蛋白质的原子模型还是细胞行为的现实模型。在许多 在某些情况下，关键事件可能发生在模拟时间尺度之外-例如蛋白质折叠， 蛋白质的构象转变、蛋白质复合物的组装或细胞行为的转变 从健康状态到病态状态。WESTPA软件包是一个强大的“Meta工具”， 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。WESTPA 控制现有的动力学引擎，编排多达数千个轨迹， 任何规模的那些包装（例如，Gromacs，Amber，BioNetGen，MCell）使用“加权系综” 战略WESTPA不仅自动并行化动力学引擎的使用， 通过添加和删除轨迹的统计过程，WESTPA可以获得估计值， 关键的动力学和平衡可观的计算时间大大少于将需要在 普通的并行化。该提案的目的是（一）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;（ii）扩展 WESTPA的基础计算能力，通过算法的改进;（iii）证明 WESTPA通过一系列从分子到细胞尺度的“展示”实例的有效性 使用各种动力学引擎。目标的完成将使调查人员，他们的 实验和计算合作者，以及世界各地的用户，使广泛的， 在多个尺度上对新兴的生物模拟领域做出了贡献。

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.