Abstract

Hydrogen bonding between amino acids and nucleobases is important for RNA–protein recognition. As a first step toward understanding the physicochemical features of these contacts, the present work employs density functional theory calculations to critically analyze the intrinsic structures and strength of all theoretically possible model hydrogen-bonded complexes involving RNA nucleobase edges and polar amino acid side chains. Our geometry optimizations uncover a number of unique complexes that involve variable hydrogen-bonding characteristics, including conventional donor–acceptor interactions, bifurcated interactions and single hydrogen-bonded contacts. Further, significant strength of these complexes in the gas phase (−27 kJ mol⁻¹ to −226 kJ mol⁻¹) and solvent phase (−19 kJ mol⁻¹ to −78 kJ mol⁻¹) points toward the ability of associated contacts to provide stability to RNA–protein complexes. More importantly, for the first time, our study uncovers the features of complexes involving protonated nucleobases, as well as those involving the weakly polar cysteine side chain, and thereby highlights their potential importance in biological processes that involve RNA–protein interactions. Additional analysis on select base pair-amino acid complexes uncovers the ability of amino acid side chain to simultaneously interact with both nucleobases of the base pair, and highlights the greater strength of such interactions compared to base-amino acid interactions. Overall, our analysis provides a basic physicochemical framework for understanding the molecular basis of nucleic acid–protein interactions. Further, our quantum chemical data can be used to design better algorithms for automated search of these contacts at the RNA–protein interface.

Communicated by Ramaswamy H. Sarma

摘要

氨基酸和核碱基之间的氢键对于RNA-蛋白质识别很重要。作为了解这些接触的物理化学特征的第一步，本工作采用密度泛函理论计算来批判性地分析所有涉及 RNA 核碱基边缘和极性氨基酸侧链的理论可能模型氢键复合物的内在结构和强度。我们的几何优化揭示了许多独特的复合物，它们涉及可变的氢键特性，包括传统的供体-受体相互作用、分叉相互作用和单氢键接触。此外，这些配合物在气相（-27 kJ mol ^-1至 -226 kJ mol ^-1）和溶剂相（-19 kJ mol^-1至 -78 kJ 摩尔^-1) 指向相关接触为 RNA-蛋白质复合物提供稳定性的能力。更重要的是，我们的研究首次揭示了涉及质子化核碱基的复合物的特征，以及涉及弱极性半胱氨酸侧链的复合物的特征，从而突出了它们在涉及 RNA-蛋白质相互作用的生物过程中的潜在重要性。对选择的碱基对-氨基酸复合物的额外分析揭示了氨基酸侧链同时与碱基对的两个核碱基相互作用的能力，并强调了与碱基-氨基酸相互作用相比，这种相互作用的强度更大。总的来说，我们的分析为理解核酸-蛋白质相互作用的分子基础提供了一个基本的物理化学框架。更远，

由 Ramaswamy H. Sarma 交流