PNNL

Abstract

The most stable structures for complexes of minor tautomers of uracil (U) with glycine (G) were characterized at the density functional B3LYP/6-31++G** level of theory. These are cyclic structures stabilized by two hydrogen bonds. The relative stability of isolated tautomers of uracil was rationalized by using thermodynamic and structural arguments. The stabilization energies for complexes between tautomers of U and G result from interplay between stabilizing two-body interaction energies and destabilizing one-body terms. The latter are related to the energies of: (i) tautomerization of the unperturbed moieties and (ii) distortions of the tautomers in the complex. The two-body term is related to the interaction energy between distorted tautomers. The two-body interaction energy term correlates with perturbations of length of the Y-H proton-donor bonds as well as with deprotonation enthalpies and proton affinities of the appropriate monomers sites. It was demonstrated that the relative instability of rare tautomers of uracil is diminished due to their interactions with glycine. In particular, the instability of the third most stable tautomer is decreased from 11.9 kcal/mol for an isolated uracil to 6.7 kcal/mol in a complex with the zwitterionic tautomer of glycine. A decrease of instability by 5.2 kcal/mol in the free enthalpy scale could result in an increase of concentration of this tautomer by almost five orders of magnitude. Such a concentration falls in the mutationally significant range. The increased stability of the third tautomer of uracil, and probably thymine, can be relevant for point mutations because its proton donor and acceptor sites are complementary with those of guanine rather than these of adenine.