Keskin O, Bahar I, Badretdinov A Y, Ptitsyn O B, Jernigan R L
Chemical Engineering Department & Polymer Research Center, Bogazici University, and TUBITAK Advanced Polymeric Materials Research Center, Istanbul, Turkey.
Protein Sci. 1998 Dec;7(12):2578-86. doi: 10.1002/pro.5560071211.
Whether knowledge-based intra-molecular inter-residue potentials are valid to represent inter-molecular interactions taking place at protein-protein interfaces has been questioned in several studies. Differences in the chain connectivity effect and in residue packing geometry between interfaces and single chain monomers have been pointed out as possible sources of distinct energetics for the two cases. In the present study, the interfacial regions of protein-protein complexes are examined to extract inter-molecular inter-residue potentials, using the same statistical methods as those previously adopted for intra-molecular residue pairs. Two sets of energy parameters are derived, corresponding to solvent-mediation and "average residue" mediation. The former set is shown to be highly correlated (correlation coefficient 0.89) with that previously obtained for inter-residue interactions within single chain monomers, while the latter exhibits a weaker correlation (0.69) with its intra-molecular counterpart. In addition to the close similarity of intra- and inter-molecular solvent-mediated potentials, they are shown to be significantly more residue-specific and thereby discriminative compared to the residue-mediated ones, indicating that solvent-mediation plays a major role in controlling the effective inter-residue interactions, either at interfaces, or within single monomers. Based on this observation, a reduced set of energy parameters comprising 20 one-body and 3 two-body terms is proposed (as opposed to the 20 x 20 tables of inter-residue potentials), which reproduces the conventional 20 x 20 tables with a correlation coefficient of 0.99.
基于知识的分子内残基间势能是否有效地代表了蛋白质-蛋白质界面处发生的分子间相互作用，这在几项研究中受到了质疑。界面和单链单体之间在链连接效应和残基堆积几何结构上的差异已被指出是这两种情况具有不同能量学的可能来源。在本研究中，使用与先前用于分子内残基对相同的统计方法，对蛋白质-蛋白质复合物的界面区域进行了研究，以提取分子间残基间势能。推导出了两组能量参数，分别对应于溶剂介导和“平均残基”介导。结果表明，前一组与先前在单链单体中获得的残基间相互作用高度相关（相关系数为0.89），而后者与其分子内对应物的相关性较弱（0.69）。除了分子内和分子间溶剂介导的势能非常相似之外，与残基介导的势能相比，它们还表现出明显更强的残基特异性和区分性，这表明溶剂介导在控制界面或单体内有效的残基间相互作用中起主要作用。基于这一观察结果，提出了一组简化的能量参数，包括20个单体项和3个二体项（与残基间势能的20×20表格相对），其再现了传统的20×20表格，相关系数为0.99。
