Hydrogen bonds and salt bridges across protein-protein interfaces
Hydrogen bonds and salt bridges across protein-protein interfaces
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DOI：
10.1093/protein/10.9.999
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发表时间：
1997-09-01
期刊：
影响因子：
--
通讯作者：
Nussinov, R
中科院分区：
文献类型：
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作者：
Xu, D;Tsai, CJ;Nussinov, R
为了进一步了解和利用蛋白质-蛋白质界面之间的相互作用，我们对源自高质量 X 射线结构的 319 个非冗余蛋白质-蛋白质界面的氢键和盐桥进行了分析，我们发现蛋白质界面上氢键的几何形状通常不太理想，并且比链内通常观察到的分布更广泛，这种差异源于埋藏在结合界面中的侧链比折叠单体内部更亲水，蛋白质折叠与蛋白质不同结合，而在折叠过程中，链几乎可以使用所有自由度来实现其最佳构型，但刚性结合则不然，蛋白质分子已经折叠，链只有六个平移和旋转自由度才能实现其最有利的结合构型。这些约束强制埋在界面中的许多极性/带电残基与蛋白质原子形成弱氢键，而不是与溶剂形成强氢键。由于界面氢键比链内氢键弱，因此与水的结合竞争，更多与蛋白质内部相比，水分子参与跨蛋白质界面的氢键网络桥接，界面水分子既介导非互补的供体-供体或受体-受体对，也连接非最佳定向的供体-受体对，界面氢键模式与链内氢键模式之间的这些差异进一步证实了刚性结合形成的蛋白质复合物可能远离整体最小构象的观点，此外，我们总结了电荷互补模式以及跨结合界面的氢键网络的保守性，我们进一步说明了本研究在理解蛋白质-蛋白质关联的特异性方面的效用，以及因此在对接预测和分子（抑制剂）设计中的效用。
To understand further, and to utilize, the interactions across protein-protein interfaces, we carried out an analysis of the hydrogen bonds and of the salt bridges in a collection of 319 non-redundant protein-protein interfaces derived from high-quality X-ray structures, We found that the geometry of the hydrogen bonds across protein interfaces is generally less optimal and has a wider distribution than typically observed within the chains, This difference originates from the more hydrophilic side chains buried in the binding interface than in the folded monomer interior, Protein folding differs from protein binding, Whereas in folding practically all degrees of freedom are available to the chain to attain its optimal configuration, this is not the case for rigid binding, where the protein molecules are already folded, with only six degrees of translational and rotational freedom available to the chains to achieve their most favorable bound configuration, These constraints enforce many polar/charged residues buried in the interface to form weak hydrogen bonds with protein atoms, rather than strongly hydrogen bonding to the solvent, Since interfacial hydrogen bonds are weaker than the intra-chain ones to compete with the binding of water, more water molecules are involved in bridging hydrogen bond networks across the protein interface than in the protein interior, Interfacial water molecules both mediate non-complementary donor-donor or acceptor-acceptor pairs, and connect non-optimally oriented donor-acceptor pairs, These differences between the interfacial hydrogen bonding patterns and the intra-chain ones further substantiate the notion that protein complexes formed by rigid binding may be far away from the global minimum conformations, Moreover, we summarize the pattern of charge complementarity and of the conservation of hydrogen bond network across binding interfaces, We further illustrate the utility of this study in understanding the specificity of protein-protein associations, and hence in docking prediction and molecular (inhibitor) design.