Ab Initio Interaction Energies of Hydrogen-Bonded Amino Acid Side Chain-Nucleic Acid Base Interactions

摘要

Hydrogen-bonding interactions often make substantial contributions to the specificity of protein-nucleic acid complexes. In a seminal study, Seeman et al. postulated that two hydrogen bonds between an amino acid side chain and base could be used to uniquely distinguish among all possible base pairs in the DNA major groove. Indeed, their predicted Arg-G and Asn/Gln-A doubly hydrogen-bonded (bidentate) interactions (Figure 1; nos. 9 and 19) are the most frequently observed in protein-nucleic acid complexes. Within RNA structures, bases also can be found in non-Watson-Crick pairs or in unpaired contexts, providing new opportunities for specific amino acid-base hydrogen-bonding interactions. Using a geometric modeling approach, we previously identified 28 possible bidentate 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.