Wepy: A Flexible Software Framework for Simulating Rare Events with Weighted Ensemble Resampling

Here, we introduce the open-source software framework wepy (https://github.com/ADicksonLab/wepy) which is a toolkit for running and analyzing weighted ensemble (WE) simulations. The wepy toolkit is in pure Python and as such is highly portable and extensible, making it an excellent platform to develop and use new WE resampling algorithms such as WExplore, REVO, and others while leveraging the entire Python ecosystem. In addition, wepy simplifies WE-specific analyses by defining out-of-core tree-like data structures using the cross-platform HDF5 file format. In this paper, we discuss the motivations and challenges for simulating rare events in biomolecular systems. As has previously been shown, high-dimensional WE resampling algorithms such as WExplore and REVO have been successful at these tasks, especially for rare events that are difficult to describe by one or two collective variables. We explain in detail how wepy facilitates implementation of these algorithms, as well as aids in analyzing the unique structure of WE simulation results. To explain how wepy and WE work in general, we describe the mathematical formalism of WE, an overview of the architecture of wepy, and provide code examples of how to construct, run, and analyze simulation results for a protein–ligand system (T4 Lysozyme in an implicit solvent). This paper is written with a variety of readers in mind, including (1) those curious about how to leverage WE rare-event simulations for their domain, (2) current WE users who want to begin using new high-dimensional resamplers such as WExplore and REVO, and (3) expert users who would like to prototype or implement their own algorithms that can be easily adopted by others.本文介绍了开源软件框架wepy（https://github.com/ADicksonLab/wepy），其作为一款用于运行和分析加权系综（Weighted Ensemble, WE）模拟的工具包。wepy工具包采用纯Python开发，具备极高的可移植性与可扩展性，可依托完整的Python生态系统，成为开发和使用WExplore、REVO等新型加权系综重采样算法的优质平台。此外，wepy通过跨平台HDF5文件格式定义核外树状数据结构，简化了针对加权系综的专属分析流程。 本文探讨了生物分子体系中稀有事件模拟的动机与挑战。已有研究表明，WExplore、REVO等高维加权系综重采样算法在这类任务中表现优异，尤其适用于难以通过一至两个集体变量描述的稀有事件。本文详细阐述了wepy如何助力这类算法的实现，并辅助分析加权系综模拟结果的独特结构。 为整体阐释wepy与加权系综的工作原理，本文将介绍加权系综的数学形式化表述、wepy的架构概览，并提供蛋白质-配体体系（隐式溶剂中的T4溶菌酶）的模拟构建、运行与结果分析代码示例。本文面向三类读者群体：其一，对如何将加权系综稀有事件模拟应用于自身研究领域感到好奇的研究者；其二，希望开始使用WExplore、REVO等新型高维重采样工具的现有加权系综用户；其三，希望开发或实现自有算法并便于他人复用的专业用户。