Department of Mechanical Engineering, University of Alberta and National Institute for Nanotechnology, 11421 Saskatchewan Dr NW, Edmonton, AB, T6G 2M9, Canada.
Department of Mathematics, College of the Canyons, Santa Clarita, CA, 91355, USA.
J Mol Model. 2017 May;23(5):167. doi: 10.1007/s00894-017-3344-6. Epub 2017 Apr 27.
This study identifies dynamical properties of maltose-binding protein (MBP) useful in unveiling active site residues susceptible to ligand binding. The described methodology has been previously used in support of novel topological techniques of persistent homology and statistical inference in complex, multi-scale, high-dimensional data often encountered in computational biophysics. Here we outline a computational protocol that is based on the anisotropic elastic network models of 14 all-atom three-dimensional protein structures. We introduce the notion of dynamical distance matrices as a measure of correlated interactions among 370 amino acid residues that constitute a single protein. The dynamical distance matrices serve as an input for a persistent homology suite of codes to further distinguish a small subset of residues with high affinity for ligand binding and allosteric activity. In addition, we show that ligand-free closed MBP structures require lower deformation energies than open MBP structures, which may be used in categorization of time-evolving molecular dynamics structures. Analysis of the most probable allosteric coupling pathways between active site residues and the protein exterior is also presented.
本研究确定了麦芽糖结合蛋白（MBP）的动力学特性，这些特性有助于揭示易与配体结合的活性位点残基。所描述的方法以前曾用于支持持久同调的新型拓扑技术和复杂、多尺度、高维数据的统计推断，这些数据在计算生物物理学中经常遇到。在这里，我们概述了一种基于 14 个全原子三维蛋白质结构各向异性弹性网络模型的计算方案。我们引入了动态距离矩阵的概念，作为构成单个蛋白质的 370 个氨基酸残基之间相关相互作用的度量。动态距离矩阵作为持久同调代码套件的输入，以进一步区分与配体结合和变构活性具有高亲和力的一小部分残基。此外，我们还表明，无配体结合的闭合 MBP 结构需要比开放 MBP 结构更低的变形能，这可用于对时变分子动力学结构进行分类。还分析了活性位点残基与蛋白质外部之间最可能的变构偶联途径。
