del Sol Antonio, O'Meara Paul
Bioinformatics Research Project, Frontier Research Division, Fujirebio Inc., 51 Komiya-cho, Hachioji-shi, Tokyo 192-0031, Japan.
Proteins. 2005 Feb 15;58(3):672-82. doi: 10.1002/prot.20348.
We show that protein complexes can be represented as small-world networks, exhibiting a relatively small number of highly central amino-acid residues occurring frequently at protein-protein interfaces. We further base our analysis on a set of different biological examples of protein-protein interactions with experimentally validated hot spots, and show that 83% of these predicted highly central residues, which are conserved in sequence alignments and nonexposed to the solvent in the protein complex, correspond to or are in direct contact with an experimentally annotated hot spot. The remaining 17% show a general tendency to be close to an annotated hot spot. On the other hand, although there is no available experimental information on their contribution to the binding free energy, detailed analysis of their properties shows that they are good candidates for being hot spots. Thus, highly central residues have a clear tendency to be located in regions that include hot spots. We also show that some of the central residues in the protein complex interfaces are central in the monomeric structures before dimerization and that possible information relating to hot spots of binding free energy could be obtained from the unbound structures.
我们表明，蛋白质复合物可表示为小世界网络，其在蛋白质 - 蛋白质界面处频繁出现相对少量的高度中心氨基酸残基。我们进一步基于一组具有经实验验证的热点的蛋白质 - 蛋白质相互作用的不同生物学实例进行分析，并表明这些预测的高度中心残基中有83%在序列比对中保守且在蛋白质复合物中不暴露于溶剂，它们对应于实验注释的热点或与实验注释的热点直接接触。其余17%总体上显示出靠近注释热点的趋势。另一方面，尽管没有关于它们对结合自由能贡献的可用实验信息，但对其性质的详细分析表明它们是热点的良好候选者。因此，高度中心残基明显倾向于位于包含热点的区域。我们还表明，蛋白质复合物界面中的一些中心残基在二聚化之前的单体结构中也是中心的，并且可以从未结合结构中获得与结合自由能热点相关的可能信息。
