Ensembler: enabling high-throughput molecular simulations at the superfamily scale

The rapidly expanding body of available genomic and protein structural data provides a rich resource for understanding protein dynamics with biomolecular simulation. While computational infrastructure has grown rapidly, simulations on an omics scale are not yet widespread, primarily because software infrastructure to enable simulations at this scale has not kept pace. It should now be possible to study protein dynamics across entire (super)families, exploiting both available structural biology data and conformational similarities across homologous proteins. Here, we present a new tool for enabling high-throughput simulation in the genomics era. Ensembler takes any set of sequences—from a single sequence to an entire superfamily—and shepherds them through various stages of modeling and refinement to produce simulation-ready structures. This includes comparative modeling to all relevant PDB structures (which may span multiple conformational states of interest), reconstruction of missing l...日益增长的公开基因组与蛋白质结构数据体量，为借助生物分子模拟解析蛋白质动态特性提供了宝贵资源。尽管计算基础设施发展迅猛，但组学尺度下的蛋白质模拟尚未普及，核心原因在于适配该规模模拟的软件基础设施未能同步发展。如今，依托已公开的结构生物学数据与同源蛋白质间的构象相似性，已能够针对完整（超）家族开展蛋白质动态特性研究。本研究在此介绍一款适配基因组学时代的高通量模拟新工具Ensembler。该工具可接收任意序列集合（从单条序列至完整（超）家族），并引导其历经建模与优化的全流程，最终生成可直接用于模拟的蛋白质结构。该流程涵盖针对所有相关PDB（Protein Data Bank）结构的比较建模（可覆盖目标蛋白的多种构象状态），以及缺失片段的重构……