PROTON-TRANSFER IN THE ADENINE-THYMINE BASE-PAIR

The transition state for the double proton transfer in the Watson-Crick type of adenine-thymine (AT) base pair was located by using the ab initio HF MINI-1 full gradient optimization technique. Allowing the geometry to relax in the calculation of the double proton transfer and interaction energies results in a substantial lowering of the energetic difference between AT and its imino-enol tautomer, A*T*. An energy barrier of 9.7 kcal/mol was calculated for the lowest energy reaction path from the canonical AT structure to the rare tautomeric A*T* structure, whereas a barrier of only 0.2 kcal/mol occurred for the reverse reaction. Although the relative energies may be affected by the theoretical level used, it is evident that there exist two energy minima which are separated by a low-lying transition state. Our results confirm the stability of the genetic code. More specifically, the possibility that proton transfer in the nucleic acid base pairs might be the cause of spontaneous point mutations in DNA and aging phenomena is not supported by the SCF/MINI-1 results for the isolated AT base pair. No minima which correspond to the zwitterionic structures A(+)T(-) and A(-)T(+) were found. The effect of basis set extension was studied by including single-point SCF/MIDI-1 calculations. In addition, we suggest a possible role of the remarkably large interaction enthalpy of the A*T* base pair formed by imino-enol tautomers in RNA-ribozyme and codon-anticodon interactions.