Mukherjee Shayantani, Majumdar Sudipta, Bhattacharyya Dhananjay
Biophysics Division, Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064, India.
J Phys Chem B. 2005 May 26;109(20):10484-92. doi: 10.1021/jp0446231.
Amino groups are one of the various types of hydrogen bond donors, abundantly found in protein main chains, protein side chains, and DNA bases. The polar hydrogen atoms of these groups exhibit short ranged, specific, and directional hydrogen bonds, which play a decisive role in the specificity and stability of protein-DNA complexes. To date, planar amino groups are only considered for the analysis of protein-DNA interfacial hydrogen bonds. This assumption regarding hydrogen atom positions possibly failed to establish the expected role of hydrogen bonds in protein-DNA recognition. We have performed ab initio quantum chemical studies on amino acid side chains and DNA bases containing amino groups as well as on specific hydrogen bonded residue pairs selected from high-resolution protein-DNA complex crystal structures. Our results suggest that occurrences of pyramidal amino groups are more probable in comparison with the usually adopted planar geometry. This increases the quality of the existing hydrogen bonds in almost all cases. Further, detailed analysis of protein-DNA interfacial hydrogen bonds in 107 crystal structures using the in-house program "pyrHBfind" indicates that consideration of energetically more preferred nonplanar amino groups improves the geometry of hydrogen bonds and also gives rise to new contacts amounting to nearly 14.5% of the existing interactions. Large improvements have been observed specifically for the amino groups of guanine, which faces the DNA minor groove and thus helps to resolve the problem of insufficient directional contacts observed in many minor groove binding complexes. Apart from guanine, improvement observed for asparagine, glutamine, adenine, or cytosine also indicates that the consideration of nonplanar amino groups leads to a more realistic scenario of hydrogen bonds occurring between protein and DNA residues.
氨基是各类氢键供体之一，在蛋白质主链、蛋白质侧链和DNA碱基中大量存在。这些基团的极性氢原子会形成短程、特定且具有方向性的氢键，它们在蛋白质 - DNA复合物的特异性和稳定性中起着决定性作用。迄今为止，在分析蛋白质 - DNA界面氢键时仅考虑平面氨基。这种关于氢原子位置的假设可能无法确定氢键在蛋白质 - DNA识别中的预期作用。我们对含有氨基的氨基酸侧链和DNA碱基以及从高分辨率蛋白质 - DNA复合物晶体结构中选取的特定氢键残基对进行了从头算量子化学研究。我们的结果表明，与通常采用的平面几何结构相比，锥形氨基出现的可能性更大。这在几乎所有情况下都提高了现有氢键的质量。此外，使用内部程序“pyrHBfind”对107个晶体结构中的蛋白质 - DNA界面氢键进行详细分析表明，考虑能量上更优的非平面氨基可以改善氢键的几何结构，还会产生相当于现有相互作用近14.5%的新接触。特别观察到鸟嘌呤的氨基有很大改善，鸟嘌呤面向DNA小沟，因此有助于解决许多小沟结合复合物中观察到的定向接触不足的问题。除了鸟嘌呤，天冬酰胺、谷氨酰胺、腺嘌呤或胞嘧啶的改善也表明，考虑非平面氨基会使蛋白质和DNA残基之间形成氢键的情况更符合实际。
