Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Proteins. 2011 Mar;79(3):898-915. doi: 10.1002/prot.22927. Epub 2011 Jan 5.
Salt bridges occur frequently in proteins, providing conformational specificity and contributing to molecular recognition and catalysis. We present a comprehensive analysis of these interactions in protein structures by surveying a large database of protein structures. Salt bridges between Asp or Glu and His, Arg, or Lys display extremely well-defined geometric preferences. Several previously observed preferences are confirmed, and others that were previously unrecognized are discovered. Salt bridges are explored for their preferences for different separations in sequence and in space, geometric preferences within proteins and at protein-protein interfaces, co-operativity in networked salt bridges, inclusion within metal-binding sites, preference for acidic electrons, apparent conformational side chain entropy reduction on formation, and degree of burial. Salt bridges occur far more frequently between residues at close than distant sequence separations, but, at close distances, there remain strong preferences for salt bridges at specific separations. Specific types of complex salt bridges, involving three or more members, are also discovered. As we observe a strong relationship between the propensity to form a salt bridge and the placement of salt-bridging residues in protein sequences, we discuss the role that salt bridges might play in kinetically influencing protein folding and thermodynamically stabilizing the native conformation. We also develop a quantitative method to select appropriate crystal structure resolution and B-factor cutoffs. Detailed knowledge of these geometric and sequence dependences should aid de novo design and prediction algorithms.
盐桥在蛋白质中经常出现，提供构象特异性，并有助于分子识别和催化。我们通过调查大量蛋白质结构数据库，对这些相互作用进行了全面分析。天冬氨酸或谷氨酸与组氨酸、精氨酸或赖氨酸之间的盐桥显示出非常明确的几何偏好。我们确认了一些以前观察到的偏好，也发现了一些以前未被识别的偏好。盐桥的偏好包括在序列和空间中的不同分离、蛋白质内和蛋白质-蛋白质界面内的几何偏好、网络盐桥的协同作用、金属结合位点的包含、对酸性电子的偏好、形成时明显的构象侧链熵减少以及掩埋程度。盐桥在近距离而非远距离序列分离的残基之间出现的频率要高得多，但在近距离时，特定分离处的盐桥仍然存在强烈的偏好。还发现了涉及三个或更多成员的特定类型的复杂盐桥。由于我们观察到形成盐桥的倾向与盐桥残基在蛋白质序列中的位置之间存在很强的关系，因此我们讨论了盐桥在动力学上影响蛋白质折叠和热力学上稳定天然构象的作用。我们还开发了一种定量方法来选择合适的晶体结构分辨率和 B 因子截止值。这些几何和序列依赖性的详细知识应该有助于从头设计和预测算法。
