posted on 2005-02-23, 00:00authored byIwona Da̧bkowska, Maciej Gutowski, Janusz Rak
The most stable structures for the gas-phase 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 the tautomers of U and G result from interplay between the 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 resulting rare tautomers in the complex. The two-body term
describes the interaction energy between distorted tautomers. The two-body interaction energy term
correlates with perturbations of length of the proton-donor bonds as well as with deprotonation enthalpies
and proton affinities of the appropriate monomer 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 (UIII) is decreased from 11.9 kcal/mol for non-interacting uracil to 6.7 kcal/mol for uracil in a complex with the zwitterionic tautomer of glycine. A decrease of instability by 5.2 kcal/mol could result in an increase of concentration of UIII by almost 5 orders of magnitude. This is the tautomer
with proton donor and acceptor sites matching guanine rather than adenine. Moreover, kinetic characteristics
obtained for the glycine-assisted conversion of the most stable tautomer of uracil (UI) to UIII indicate that
the UI↔UIII thermodynamic equilibrium could be easily attained at room temperature. The resulting
concentration of this tautomer falls in a mutationally significant range.