High-performance weighted ensemble software for simulation of complex bio-events

用于复杂生物事件模拟的高性能加权集成软件(Renewal) 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时间 模拟，无论是蛋白质的原子模型，还是细胞行为的真实模型。在许多 在某些情况下，关键事件可能发生在模拟时间范围之外--例如蛋白质折叠， 蛋白质的构象转变、蛋白质复合体的组装或细胞行为的转变 从健康到病态。WESTPA软件包是一个强大的“元工具”，它可以 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 通过协调多达数千条由本机运行的轨迹来控制现有的动力学引擎 任何规模的套餐(如Gromacs、Amber、BioNetGen、Mcell)，使用“加权组合” 策略。WESTPA不仅自动并行化了动力学引擎的使用，而且因为 在添加和删除轨迹的统计过程中，WESTPA可以获得估计 关键动力学和平衡观测值的计算时间大大少于 普通并行化。该提案的目的是(I)为云计算优化WESTPA， 提高易用性，并开发高度可扩展的数据存储分析；(Ii)扩展 WESTPA通过算法改进的基本计算能力；以及(Iii)演示 WESTPA的有效性通过一系列从分子到细胞尺度的“展示”例子 使用了各种动力引擎。这些目标的完成将使调查人员能够 实验和计算合作者，以及世界各地的用户 在多个尺度上对生物模拟这一新兴领域的贡献。

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.