Towse Clare-Louise, Rysavy Steven J, Vulovic Ivan M, Daggett Valerie
Department of Bioengineering, University of Washington, Box 355013, Seattle, WA 98195-5013, USA.
Biomedical and Health Informatics Program, University of Washington, Box 355013, Seattle, WA 98195-5013, USA.
Structure. 2016 Jan 5;24(1):187-199. doi: 10.1016/j.str.2015.10.017.
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 × 10(9) rotamers, 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.
大多数旋转异构体库是从蛋白质数据银行（PDB）的子集中生成的，不能完全代表蛋白质侧链的构象范围。以前纠正这种对构象空间稀疏覆盖的尝试涉及应用加权和平滑函数。我们通过使用基于物理的分子动力学模拟来确定旋转异构体状态更准确的频率，从而解决了这些限制。这项工作是我们动态组学计划的一部分，使用了一组807种蛋白质，这些蛋白质被选来代表97%的已知自主蛋白质折叠，从而消除了PDB中常见拓扑结构的偏差。我们从动态组学得出的旋转异构体库包含4.8×10⁹个旋转异构体，从93642个残基中每个残基至少51000次出现中采样得到。在这里，我们提供了一个基于二级结构ϕ/ψ区域的依赖主链的旋转异构体库，以及对我们2011年不依赖主链的库的更新，该更新解决了自其最初发表以来我们数据集翻倍的问题。
