title: Ab initio interaction energies of hydrogen-bonded amino acid side chain[bond]nucleic acid base interactions.
abstract: 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.
authors.affiliation: Department of Biochemistry and Biophysics and Graduate Group in Biophysics, University of California, San Francisco, California 94143-0448, USA.
authors.forename: Alan C
authors.initials: AC
authors.lastname: Cheng
authors.forename: Alan D
authors.initials: AD
authors.lastname: Frankel
mesh_terms: D000225:Adenine / Q000737:chemistry* / Q000378:metabolism; D000596:Amino Acids / Q000737:chemistry* / Q000378:metabolism; D003596:Cytosine / Q000737:chemistry* / Q000378:metabolism; D006147:Guanine / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D013816:Thermodynamics; D014498:Uracil / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000596:Amino Acids; D014498:Uracil; D006147:Guanine; D003596:Cytosine; D000225:Adenine