Center for Bioinformatics, The University of Kansas, Lawrence, KS 66047, USA.
BMC Bioinformatics. 2012 Sep 17;13:236. doi: 10.1186/1471-2105-13-236.
Protein interactions play a key role in life processes. Characterization of conformational properties of protein-protein interactions is important for understanding the mechanisms of protein association. The rapidly increasing amount of experimentally determined structures of proteins and protein-protein complexes provides foundation for research on protein interactions and complex formation. The knowledge of the conformations of the surface side chains is essential for modeling of protein complexes. The purpose of this study was to analyze and compare dihedral angle distribution functions of the side chains at the interface and non-interface areas in bound and unbound proteins.
To calculate the dihedral angle distribution functions, the configuration space was divided into grid cells. Statistical analysis showed that the similarity between bound and unbound interface and non-interface surface depends on the amino acid type and the grid resolution. The correlation coefficients between the distribution functions increased with the grid spacing increase for all amino acid types. The Manhattan distance showing the degree of dissimilarity between the distribution functions decreased accordingly. Short residues with one or two dihedral angles had higher correlations and smaller Manhattan distances than the longer residues. Met and Arg had the slowest growth of the correlation coefficient with the grid spacing increase. The correlations between the interface and non-interface distribution functions had a similar dependence on the grid resolution in both bound and unbound states. The interface and non-interface differences between bound and unbound distribution functions, caused by biological protein-protein interactions or crystal contacts, disappeared at the 70° grid spacing for interfaces and 30° for non-interface surface, which agrees with an average span of the side-chain rotamers.
The two-fold difference in the critical grid spacing indicates larger conformational changes upon binding at the interface than at the rest of the surface. At the same time, transitions between rotamers induced by interactions across the interface or the crystal packing are rare, with most side chains having local readjustments that do not change the rotameric state. The analysis is important for better understanding of protein interactions and development of flexible docking approaches.
蛋白质相互作用在生命过程中起着关键作用。蛋白质-蛋白质相互作用构象特性的表征对于理解蛋白质缔合的机制很重要。大量实验确定的蛋白质和蛋白质-蛋白质复合物结构的快速增长为研究蛋白质相互作用和复合物形成提供了基础。表面侧链构象的知识对于蛋白质复合物的建模至关重要。本研究的目的是分析和比较结合和未结合蛋白质中界面和非界面区域的侧链二面角分布函数。
为了计算二面角分布函数，将构象空间划分为网格单元。统计分析表明，结合和未结合界面和非界面表面之间的相似性取决于氨基酸类型和网格分辨率。对于所有氨基酸类型，分布函数之间的相关系数随着网格间距的增加而增加。显示分布函数之间差异程度的曼哈顿距离相应减小。具有一个或两个二面角的短残基比长残基具有更高的相关性和更小的曼哈顿距离。Met 和 Arg 与网格间距增加的相关性增长最慢。在结合和未结合状态下，界面和非界面分布函数之间的相关性具有相似的网格分辨率依赖性。结合和未结合状态下，由生物蛋白质-蛋白质相互作用或晶体接触引起的界面和非界面分布函数之间的差异，在界面处的 70°网格间距和非界面处的 30°网格间距处消失，这与侧链构象的平均跨度一致。
界面处结合时的临界网格间距的两倍差异表明构象变化较大，而在其余表面处的构象变化较小。同时，界面或晶体包装相互作用引起的构象转变很少见，大多数侧链发生局部调整而不改变构象状态。该分析对于更好地理解蛋白质相互作用和开发灵活对接方法很重要。
