Strong and weak hydrogen bonds in the protein-ligand interface
Strong and weak hydrogen bonds in the protein-ligand interface
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DOI：
10.1002/prot.21253
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发表时间：
2007-04-01
影响因子：
2.9
通讯作者：
Desiraju, Gautam R.
中科院分区：
文献类型：
--
作者：
Panigrahi, Sunil K.;Desiraju, Gautam R.
利用内部开发的新的计算机程序，分析了251个蛋白质-配体复合体的N-H中心点O、O-H中心点O和C-H中心点O氢键的特征以及其他弱的分子间相互作用。本研究中考察的相互作用是发生在活性中心的那些相互作用，这里定义为围绕配体的半径为10埃的球体。值得注意的是，N-H中心点O和O-H中心点O键趋向于线性。多分支相互作用尤其常见，特别是多分支受体，每个分支受体的平均分支度为2.6个氢键。这项研究的一个重要方面是，我们已经能够评估氢键几何形状作为结晶学分辨率的函数的可靠性。对于强氢键和弱氢键，设定了2.3埃和2.0埃的阈值，低于这个阈值可以安全地考虑氢键几何结构进行详细分析。水作为给体或受体，C-H中心点O键与甘氨酸和酪氨酸作为给体的相互作用在活性中心普遍存在。在一组属于蛋白激酶家族的233个蛋白质-配体复合体的外部测试中也观察到了类似的趋势。还研究了较弱的相互作用，如X-H中心点pi(X=C，N，O)和以卤素原子为亲电剂或亲核剂的相互作用。我们的结论是，在蛋白质-配体识别中，强氢键和弱氢键是普遍存在的，利用合适的计算工具，可以可靠地分析配体-蛋白质界面上大量的强和弱分子间相互作用。结果证实了我们之前报告的趋势，但目前数据集的扩展性质意味着观察到的趋势更可靠。蛋白质2007；67：128-141。(C)2007年Wiley-Liss，Inc.
The characteristics of N-H center dot center dot center dot O, O-H center dot center dot center dot O, and C-H center dot center dot center dot O hydrogen bonds and other weak intermolecular interactions are analyzed in a large and diverse group of 251 protein-ligand complexes using a new computer program that was developed in-house for this purpose. The interactions examined in the present study are those which occur in the active sites, defined here as a sphere of 10 angstrom radius around the ligand. Notably, N-H center dot center dot center dot O and O-H center dot center dot center dot O bonds tend towards linearity. Multifurcated interactions are especially common, especially multifureated acceptors, and the average degree of furcation is 2.6 hydrogen bonds per furcated acceptor. A significant aspect of this study is that we have been able to assess the reliability of hydrogen bond geometry as a function of crystallographic resolution. Thresholds of 2.3 and 2.0 angstrom are established for strong and weak hydrogen bonds, below which hydrogen bond geometries may be safely considered for detailed analysis. Interactions involving water as donor or acceptor, and C-H center dot center dot center dot O bonds with Gly and Tyr as donors are ubiquitous in the active site. A similar trend was observed in an external test set of 233 protein-ligand complexes belonging to the kinase family. Weaker interactions like X-H center dot center dot center dot pi (X = C, N, O) and those involving halogen atoms as electrophiles or nucleophiles have also been studied. We conclude that the strong and weak hydrogen bonds are ubiquitous in protein-ligand recognition, and that with suitable computational tools very large numbers of strong and weak intermolecular interactions in the ligand-protein interface may be analyzed reliably. Results confirm earlier trends reported previously by us but the extended nature of the present data set mean that the observed trends are more reliable. Proteins 2007;67:128-141. (c) 2007 Wiley-Liss, Inc.