Cheng Alan C, Frankel Alan D
Department of Biochemistry and Biophysics and Graduate Group in Biophysics, University of California, San Francisco, California 94143-0448, USA.
J Am Chem Soc. 2004 Jan 21;126(2):434-5. doi: 10.1021/ja037264g.
Hydrogen-bonding interactions often make substantial contributions to the specificity of protein-nucleic acid complexes. Using a geometric modeling approach, we previously identified 28 possible doubly hydrogen-bonded interactions to the four unpaired RNA bases. Here we present interaction energies of these models, calculated by ab initio quantum chemical methods, and describe a correlation between the computed energies and observed frequencies of the interactions. In general, interactions with charged side chains show the most favorable energies. An Asp/Glu-G interaction may be especially favorable for recognition of unpaired guanines in RNAs. Asn and Ser/Thr/Tyr side chains are calculated to make iso-energetic interactions to the Hoogsteen face of adenine, but Asn-A interactions are much more common with DNA than RNA, and Ser/Thr/Tyr-A interactions are more common with RNA than DNA. Examination of the known interactions suggests that Ser/Thr/Tyr may be accommodated in a wider variety of protein contexts at RNA-protein interfaces. With these calculated intrinsic affinities, it should be possible to better assess the contributions of bidentate hydrogen-bonding interactions to RNA- and DNA-binding specificity.
氢键相互作用通常对蛋白质 - 核酸复合物的特异性有重大贡献。我们之前使用几何建模方法确定了与四个未配对RNA碱基的28种可能的双氢键相互作用。在此，我们展示了通过从头算量子化学方法计算得到的这些模型的相互作用能，并描述了计算出的能量与观察到的相互作用频率之间的相关性。一般来说，与带电荷侧链的相互作用显示出最有利的能量。天冬氨酸/谷氨酸 - 鸟嘌呤相互作用对于识别RNA中未配对的鸟嘌呤可能特别有利。计算表明，天冬酰胺以及丝氨酸/苏氨酸/酪氨酸侧链与腺嘌呤的Hoogsteen面形成等能相互作用，但天冬酰胺 - 腺嘌呤相互作用在与DNA结合时比与RNA结合时更为常见，而丝氨酸/苏氨酸/酪氨酸 - 腺嘌呤相互作用在与RNA结合时比与DNA结合时更为常见。对已知相互作用的研究表明，在RNA - 蛋白质界面处，丝氨酸/苏氨酸/酪氨酸可能存在于更广泛的蛋白质环境中。有了这些计算出的内在亲和力，应该能够更好地评估双齿氢键相互作用对RNA和DNA结合特异性的贡献。
