New Dynamic Rotamer Libraries: Data-Driven Analysis of Side-Chain Conformational Propensities.
New Dynamic Rotamer Libraries: Data-Driven Analysis of Side-Chain Conformational Propensities.
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新的动态旋转异构体库：侧链构象倾向的数据驱动分析。
DOI：
10.1016/j.str.2015.10.017
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Daggett,Valerie
中科院分区：
文献类型：
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作者：
Towse,Clare-Louise;Rysavy,StevenJ;Vulovic,IvanM;Daggett,Valerie
大多数旋转异构体文库是从PDB的子集产生的，并且不完全代表蛋白质侧链的构象范围。以前的尝试，以纠正这种稀疏覆盖的构象空间涉及应用程序的加权和平滑功能。我们解决了这些限制，使用基于物理的分子动力学模拟，以确定更准确的频率旋转异构状态。这项工作是我们Dynameomics计划的一部分，并使用一组807种蛋白质来代表97%的已知自主蛋白质折叠，从而消除了对PDB中常见拓扑结构的偏见。我们的Dynameomics衍生的旋转异构体库包含4.8 × 109个旋转异构体，从93，642个残基中的每一个至少51，000次出现中取样。在这里，我们提供了一个骨架依赖的旋转异构体库，基于二级结构的α/β区域，并更新我们的2011年骨架独立的库，解决了我们的数据集，因为它的原始出版物的两倍。
Most rotamer libraries are generated from subsets of the PDB and do not fully represent the conformational scope of protein side chains. Previous attempts to rectify this sparse coverage of conformational space have involved application of weighting and smoothing functions. We resolve these limitations by using physics-based molecular dynamics simulations to determine more accurate frequencies of rotameric states. This work forms part of our Dynameomics initiative and uses a set of 807 proteins selected to represent 97% of known autonomous protein folds, thereby eliminating the bias toward common topologies found within the PDB. Our Dynameomics derived rotamer libraries encompass 4.8 × 109rotamers, sampled from at least 51,000 occurrences of each of 93,642 residues. Here, we provide a backbone-dependent rotamer library, based on secondary structure ϕ/ψ regions, and an update to our 2011 backbone-independent library that addresses the doubling of our dataset since its original publication.