Melvin Ryan L, Xiao Jiajie, Godwin Ryan C, Berenhaut Kenneth S, Salsbury Freddie R
Department of Physics, Wake Forest University, Winston Salem, North Carolina.
Department of Mathematics and Statistics, Wake Forest University, Winston-Salem, North Carolina, 27109.
Protein Sci. 2018 Jan;27(1):62-75. doi: 10.1002/pro.3268. Epub 2017 Sep 6.
Correlated motion analysis provides a method for understanding communication between and dynamic similarities of biopolymer residues and domains. The typical equal-time correlation matrices-frequently visualized with pseudo-colorings or heat maps-quickly convey large regions of highly correlated motion but hide more subtle similarities of motion. Here we propose a complementary method for visualizing correlations within proteins (or general biopolymers) that quickly conveys intuition about which residues have a similar dynamic behavior. For grouping residues, we use the recently developed non-parametric clustering algorithm HDBSCAN. Although the method we propose here can be used to group residues using correlation as a similarity matrix-the most straightforward and intuitive method-it can also be used to more generally determine groups of residues which have similar dynamic properties. We term these latter groups "Dynamic Domains", as they are based not on spatial closeness but rather closeness in the column space of a correlation matrix. We provide examples of this method across three human proteins of varying size and function-the Nf-Kappa-Beta essential modulator, the clotting promoter Thrombin and the mismatch repair protein (dimer) complex MutS-alpha. Although the examples presented here are from all-atom molecular dynamics simulations, this visualization technique can also be used on correlations matrices built from any ensembles of conformations from experiment or computation.
相关运动分析提供了一种理解生物聚合物残基和结构域之间的通信以及动态相似性的方法。典型的等时相关矩阵——通常用伪彩色或热图可视化——能快速传达高度相关运动的大区域,但隐藏了更细微的运动相似性。在这里,我们提出了一种用于可视化蛋白质(或一般生物聚合物)内部相关性的补充方法,该方法能快速传达关于哪些残基具有相似动态行为的直观信息。为了对残基进行分组,我们使用了最近开发的非参数聚类算法HDBSCAN。虽然我们这里提出的方法可以使用相关性作为相似性矩阵来对残基进行分组——这是最直接和直观的方法——但它也可以更广泛地用于确定具有相似动态特性的残基组。我们将后者这些组称为“动态结构域”,因为它们不是基于空间接近度,而是基于相关矩阵列空间中的接近度。我们在三种大小和功能各异的人类蛋白质——核因子κB必需调节剂、凝血促进剂凝血酶和错配修复蛋白(二聚体)复合物MutS-α——上展示了该方法的示例。虽然这里给出的示例来自全原子分子动力学模拟,但这种可视化技术也可用于由实验或计算得到的任何构象集合构建的相关矩阵。