Ruvinsky Anatoly M, Kirys Tatsiana, Tuzikov Alexander V, Vakser Ilya A
Center for Bioinformatics, University of Kansas, Lawrence, KS 66047, USA.
J Bioinform Comput Biol. 2012 Apr;10(2):1241002. doi: 10.1142/S0219720012410028.
Structure fluctuations and conformational changes accompany all biological processes involving macromolecules. The paper presents a classification of protein residues based on the normalized equilibrium fluctuations of the residue centers of mass in proteins and a statistical analysis of conformation changes in the side-chains upon binding. Normal mode analysis and an elastic network model were applied to a set of protein complexes to calculate the residue fluctuations and develop the residue classification. Comparison with a classification based on normalized B-factors suggests that the B-factors may underestimate protein flexibility in solvent. Our classification shows that protein loops and disordered fragments are enriched with highly fluctuating residues and depleted with weakly fluctuating residues. Strategies for engineering thermostable proteins are discussed. To calculate the dihedral angles distribution functions, the configuration space was divided into cells by a cubic grid. The effect of protein association on the distribution functions depends on the amino acid type and a grid step in the dihedral angles space. The changes in the dihedral angles increase from the near-backbone dihedral angle to the most distant one, for most residues. On average, one fifth of the interface residues change the rotamer state upon binding, whereas the rest of the interface residues undergo local readjustments within the same rotamer.
结构波动和构象变化伴随着所有涉及大分子的生物过程。本文基于蛋白质中残基质心的归一化平衡波动对蛋白质残基进行了分类，并对结合时侧链的构象变化进行了统计分析。应用正常模式分析和弹性网络模型对一组蛋白质复合物进行计算，以确定残基波动并建立残基分类。与基于归一化B因子的分类比较表明，B因子可能低估了蛋白质在溶剂中的灵活性。我们的分类显示，蛋白质环和无序片段富含高波动残基，而低波动残基较少。文中讨论了构建热稳定蛋白质的策略。为了计算二面角分布函数，通过立方网格将构型空间划分为单元格。蛋白质缔合对分布函数的影响取决于氨基酸类型和二面角空间中的网格步长。对于大多数残基，二面角的变化从靠近主链的二面角到最远的二面角逐渐增加。平均而言，五分之一的界面残基在结合时改变了旋转异构体状态，而其余界面残基则在同一旋转异构体内进行局部重新调整。
