Xu D, Lin S L, Nussinov R
Laboratory of Mathematical Biology, SAIC Frederick NCI-FCRDC, MD 21702-1201, USA.
J Mol Biol. 1997 Jan 10;265(1):68-84. doi: 10.1006/jmbi.1996.0712.
The role of hydrophilic bridges between charged, or polar, atoms in protein associations has been examined from two perspectives. First, statistical analysis has been carried out on 21 data sets to determine the relationship between the binding free energy and the structure of the protein complexes. We find that the number of hydrophilic bridges across the binding interface shows a strong positive correlation with the free energy; second, the electrostatic contribution of salt bridges to binding has been assessed by a continuum electrostatics calculation. In contrast to protein folding, we find that salt bridges across the binding interface can significantly stabilize complexes in some cases. The different contributions of hydrophilic bridges to folding and to binding arise from the different environments to which the involved hydrophilic groups are exposed before and after the bridges are formed. These groups are more solvated in a denatured protein before folding than on the surface of the combining proteins before binding. After binding, they are buried in an environment whose residual composition can be much more hydrophilic than the one after folding. As a result, the desolvation cost of a hydrophilic pair is lower, and the favorable interactions between the hydrophilic pair and its surrounding residues are generally stronger in binding than in folding. These results complement our recent finding that while hydrophobic effect in protein-protein interfaces is significant, it is not as strong as that observed in the interior of monomers. Taken together, these studies suggest that while the types of forces in protein-protein interaction and in protein folding are similar, their relative contributions differ. Hence, association of protein monomers which do not undergo significant conformational change upon binding differs from protein folding, implying that conclusions (e.g. statistics, energetics) drawn from investigating folding may not apply directly to binding, and vice versa.
带电或极性原子间的亲水性桥在蛋白质缔合中的作用已从两个角度进行了研究。首先，对21个数据集进行了统计分析，以确定结合自由能与蛋白质复合物结构之间的关系。我们发现跨越结合界面的亲水性桥的数量与自由能呈强正相关；其次，通过连续介质静电计算评估了盐桥对结合的静电贡献。与蛋白质折叠不同，我们发现跨越结合界面的盐桥在某些情况下可显著稳定复合物。亲水性桥对折叠和结合的不同贡献源于形成桥之前和之后所涉及的亲水基团所处的不同环境。这些基团在折叠前的变性蛋白质中比在结合前的结合蛋白表面更易被溶剂化。结合后，它们被埋入的环境的残余组成可能比折叠后的环境更具亲水性。因此，亲水对的去溶剂化成本较低，并且亲水对与其周围残基之间的有利相互作用在结合中通常比在折叠中更强。这些结果补充了我们最近的发现，即虽然蛋白质 - 蛋白质界面中的疏水效应很显著，但不如在单体内部观察到的那么强。综上所述，这些研究表明，虽然蛋白质 - 蛋白质相互作用和蛋白质折叠中的作用力类型相似，但其相对贡献不同。因此，结合时不发生显著构象变化的蛋白质单体的缔合不同于蛋白质折叠，这意味着从研究折叠得出的结论（例如统计学、能量学）可能不适用于结合，反之亦然。
