A quantum chemical view of the interaction of RNA nucleobases and base pairs with the side chains of polar amino acids

• Published in: Journal of biomolecular structure & dynamics Vol. 39; no. 15; pp. 5411 - 5426
• Main Authors: Ohri, Ashita, P. Seelam, Preethi, Sharma, Purshotam
• Format: Journal Article
• Language: English
• Published: Taylor & Francis 02.09.2021
• Subjects: hydrogen bonding; nucleobase edges; Polar amino acid; quantum chemical calculations; RNA-protein contacts
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2020.1787225

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