Department of Biochemistry, University of Washington, Seattle, Washington 98195-5013, USA.
Protein Sci. 2011 Feb;20(2):341-52. doi: 10.1002/pro.565.
We have recently completed systematic molecular dynamics simulations of 807 different proteins representing 95% of the known autonomous protein folds in an effort we refer to as Dynameomics. Here we focus on the analysis of side chain conformations and dynamics to create a dynamic rotamer library. Overall this library is derived from 31,000 occurrences of each of 86,217 different residues, or 2.7 × 10(9) rotamers. This dynamic library has 74% overlap of rotamer distributions with rotamer libraries derived from static high-resolution crystal structures. Seventy-five percent of the residues had an assignable primary conformation, and 68% of the residues had at least one significant alternate conformation. The average correlation time for switching between rotamers ranged from 22 ps for Met to over 8 ns for Cys; this time decreased 20-fold on the surface of the protein and modestly for dihedral angles further from the main chain. Side chain S(2) axis order parameters were calculated and they correlated well with those derived from NMR relaxation experiments (R = 0.9). Relationships relating the S(2) axis order parameters to rotamer occupancy were derived. Overall the Dynameomics rotamer library offers a comprehensive depiction of side chain rotamer preferences and dynamics in solution, and more realistic distributions for dynamic proteins in solution at ambient temperature than libraries derived from crystal structures, in particular charged surface residues are better represented. Details of the rotamer library are presented here and the library itself can be downloaded at http://www.dynameomics.org.
我们最近完成了 807 种不同蛋白质的系统分子动力学模拟，这些蛋白质代表了已知自主蛋白质折叠的 95%，我们称之为 Dynameomics。在这里，我们专注于侧链构象和动力学的分析，以创建动态构象库。总体而言，该库源自 31,000 次 86,217 种不同残基的每种出现，或 2.7×10(9)个构象。与从静态高分辨率晶体结构中得出的构象库相比，该动态库的构象分布重叠了 74%。75%的残基具有可分配的主要构象，68%的残基具有至少一种重要的替代构象。构象之间切换的平均相关时间范围从 Met 的 22 ps 到 Cys 的超过 8 ns；在蛋白质表面，这个时间减少了 20 倍，对于远离主链的二面角则略有减少。计算了侧链 S(2)轴序参数，它们与从 NMR 弛豫实验中得出的参数很好地相关（R = 0.9）。还推导出了将 S(2)轴序参数与构象占有率相关联的关系。总体而言，Dynameomics 构象库提供了在溶液中侧链构象偏好和动力学的全面描述，并且比从晶体结构中得出的构象库更能真实地描述溶液中动态蛋白质，特别是带电荷的表面残基的分布更好。这里介绍了构象库的详细信息，该库本身可以在 http://www.dynameomics.org 下载。
