Pan Patricia Wang, Gordon Heather L, Rothstein Stuart M
Department of Chemistry, Brock University, St. Catharines, Ontario L2S 3A1, Canada.
J Chem Phys. 2006 Jan 14;124(2):024905. doi: 10.1063/1.2151174.
Global measures of structural diversity within a distribution of biopolymers, such as the radius of gyration and percent native contacts, have proven useful in the analysis of simulation data for protein folding. In this paper we describe a statistical-based methodology to quantify the local structural variability of a distribution of biopolymers, applied to 46- and 69-"residue" off-lattice, three-color model proteins. Each folds into beta-barrel structures. First we perform a principal component analysis of all interbead distance variables for a large number of independent, converged Boltzmann-distributed samples of conformations collected at each of a wide range of temperatures. Next, the principal component vectors are subjected to orthogonal (varimax) rotation. The results are displayed on so-called "squared-loading" plots. These provide a quantitative measure of the contribution to the sample variance of the position of each residue relative to the others. Dominant structural elements, those having the largest structural diversity within the sampled distribution, are responsible for peaks and shoulders observed in the specific heat versus temperature curves, generated using the weighted histogram analysis method. The loading plots indicate that the local-structural diversity of these systems changes gradually with temperature through the folding transition but radically changes near the collapse transition temperature. The analysis of the structural overlap order statistic suggests that the 46-mer thermodynamic folding transition involves the native state and at least three other nearly native intermediates. In the case of the 46-mer protein model, data are generated at sufficiently low temperatures that squared-loading plots, coupled with cluster analysis, provide a local and energetic description of its glassy state.
生物聚合物分布内结构多样性的全局度量，如回转半径和天然接触百分比，已被证明在蛋白质折叠模拟数据的分析中很有用。在本文中，我们描述了一种基于统计的方法来量化生物聚合物分布的局部结构变异性，该方法应用于46残基和69残基的非晶格三色模型蛋白质。每种蛋白质都折叠成β桶结构。首先，我们对大量在广泛温度范围内收集的独立、收敛的玻尔兹曼分布构象样本的所有珠子间距离变量进行主成分分析。接下来，对主成分向量进行正交（方差最大化）旋转。结果显示在所谓的“平方载荷”图上。这些图提供了每个残基相对于其他残基位置对样本方差贡献的定量度量。主导结构元素，即在采样分布中具有最大结构多样性的元素，是使用加权直方图分析方法生成的比热与温度曲线中观察到的峰和肩的原因。载荷图表明，这些系统的局部结构多样性在折叠转变过程中随温度逐渐变化，但在塌缩转变温度附近发生剧烈变化。结构重叠序统计量的分析表明，46聚体的热力学折叠转变涉及天然态和至少其他三个近天然中间体。在46聚体蛋白质模型的情况下，在足够低的温度下生成数据，平方载荷图与聚类分析相结合，提供了其玻璃态的局部和能量描述。
