Protein structures are stabilized by different types of hydrogen bonds. However, unlike the DNA double helical structure, the N–H···N type of hydrogen bonds is relatively rare in proteins. N–H···N hydrogen bonds formed by imidazole groups of two histidine residues have not been investigated. We have systematically analyzed 5333 high-resolution protein structures with resolution 1.8 Å or better and identified 285 histidine pairs in which the nitrogen atoms of the imidazole side chains can potentially participate in N–H···N hydrogen bonds. The histidine pairs were further divided into two groups, neutral–neutral and protonated–neutral, depending on the protonation state of the donor histidine. Quantum chemical calculations were performed on imidazole groups adopting the same geometry observed in the protein structures. Average interaction energies between the interacting imidazole groups are −6.45 and −22.5 kcal/mol for neutral–neutral and protonated–neutral, respectively. Hydrogen bond interaction between the imidazole moieties is further confirmed by natural bond orbital analyses of the model compounds. Histidine residues involved in N–H···N hydrogen bonds are relatively more buried and have low B-factor values in the protein structures. N–H···N hydrogen bond formed by a pair of buried histidine residues can significantly contribute to the structural stability of proteins.

中文翻译：

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参与蛋白质结构中N–H···N氢键的两个组氨酸残基的咪唑氮：结构生物信息学方法与量子化学计算相结合

蛋白质结构通过不同类型的氢键得以稳定。但是，与DNA的双螺旋结构不同，蛋白质中N–H···N型氢键相对较少。尚未研究由两个组氨酸残基的咪唑基形成的N–H···N氢键。我们已经系统地分析了分辨率为1.8Å或更高的5333个高分辨率蛋白质结构，并确定了285个组氨酸对，其中咪唑侧链的氮原子可以潜在地参与N·H··N氢键。根据供体组氨酸的质子化状态，将组氨酸对进一步分为两组：中性-中性和质子化-中性。对咪唑基团进行量子化学计算，采用在蛋白质结构中观察到的相同几何形状。对于中性-中性和质子化-中性，相互作用的咪唑基团之间的平均相互作用能分别为-6.45和-22.5 kcal / mol。咪唑基团之间的氢键相互作用通过模型化合物的自然键轨道分析得到进一步证实。与N·H···N氢键有关的组氨酸残基相对较埋藏且低蛋白质结构中的B因子值。由一对掩埋的组氨酸残基形成的N–H··N氢键可显着促进蛋白质的结构稳定性。