Proteins and their complexes can be heterogeneously disordered. In ensemble modeling of such systems with restraints from several experimental techniques the following problems arise: (a) integration of diverse restraints obtained on different samples under different conditions; (b) estimation of a realistic ensemble width; (c) sufficient sampling of conformational space; (d) representation of the ensemble by an interpretable number of conformers; (e) recognition of weak order with site resolution. Here, I introduce several tools that address these problems, focusing on utilization of distance distribution information for estimating ensemble width. The RigiFlex approach integrates such information with high‐resolution structures of ordered domains and small‐angle scattering data. The EnsembleFit module provides moderately sized ensembles by fitting conformer populations and discarding conformers with low population. EnsembleFit balances the loss in fit quality upon combining restraint subsets from different techniques. Pair correlation analysis for residues and local compaction analysis help in feature detection. The RigiFlex pipeline is tested on data simulated from the structure 70 kDa protein‐RNA complex RsmE/RsmZ. It recovers this structure with ensemble width and difference from ground truth both being on the order of 4.2 Å. EnsembleFit reduces the ensemble of the proliferating‐cell‐nuclear‐antigen‐associated factor p15^PAF from 4,939 to 75 conformers while maintaining good fit quality of restraints. Local compaction analysis for the PaaA2 antitoxin from E. coli O157 revealed correlations between compactness and enhanced residual dipolar couplings in the original NMR restraint set.

中文翻译：

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MMM：集成集成建模和集成分析

蛋白质及其复合物可能异质性紊乱。在使用几种实验技术进行约束的系统集成建模中，出现以下问题：（a）在不同条件下对不同样本获得的各种约束进行积分；（b）估算实际合奏宽度；（c）充分采样构象空间；（d）用可解释数量的构象者表示集合体；（e）通过现场分辨率识别弱订单。在这里，我将介绍一些解决这些问题的工具，重点是利用距离分布信息来估计整体宽度。RigiFlex方法将此类信息与有序域的高分辨率结构和小角度散射数据集成在一起。EnsembleFit模块通过拟合构象体数量并丢弃低构象体来提供中等大小的合奏。通过组合来自不同技术的约束子集，EnsembleFit可以平衡拟合质量的损失。残差对关联分析和局部压实分析有助于特征检测。RigiFlex管线已根据70 kDa蛋白质-RNA复合体RsmE / RsmZ的模拟数据进行了测试。它以整体宽度和与地面真相的差异均为4.2Å的程度恢复了该结构。EnsembleFit减少了增殖细胞核抗原相关因子p15的集合 残差对关联分析和局部压实分析有助于特征检测。RigiFlex管线已根据70 kDa蛋白质-RNA复合体RsmE / RsmZ的模拟数据进行了测试。它以整体宽度和与地面真相的差异均为4.2Å的程度恢复了该结构。EnsembleFit减少了增殖细胞核抗原相关因子p15的集合 残差对关联分析和局部压实分析有助于特征检测。RigiFlex管线已根据70 kDa蛋白质-RNA复合体RsmE / RsmZ的模拟数据进行了测试。它以整体宽度和与地面真相的差异均为4.2Å的程度恢复了该结构。EnsembleFit减少了增殖细胞核抗原相关因子p15的集合^PAF从4,939到75符合者，同时保持良好的约束适合质量。对来自大肠杆菌O157的PaaA2抗毒素的局部压实分析显示，压实与原始NMR抑制集中增强的残留偶极偶合之间存在相关性。