Complexes of pentahydrated Zn2+ with guanine, adenine, and the guanine-cytosine and adenine-thymine base pairs.: Structures and energies characterized by polarizable molecular mechanics and ab initio calculations

We investigate the binding of Zn2+ and pentahydrated Zn2+ to guanine and adenine and to the Watson-Crick G-C and A-T base pairs using the SIBFA molecular mechanics and ab initio Hartree-Fock and MP2, as well as density functional theory approaches. The ab initio computations use four basis sets: a 4-31G+(2d) coreless effective potential, the 6-31G* basis set combined with a pseudopotential description of the zinc cation, and the 6-311G** and 6-31G+(2d,2p) basis sets. For the G and G-C complexes, our computations show that the previously published structures were not global minima on the potential energy surface. The calculations demonstrate a very significant flexibility in the modes of binding of hydrated Zn2+ to nucleobases. This cation can adopt coordination numbers in the 4-6 range and bind to either N-7 or O-6 while the binding energies vary by small amounts. The SIBFA computations can reproduce the values of the ab initio binding energies using the CEP 4-31G+(2d) with an accuracy of 3% and can correctly account for the significant cooperative character (-15 kcal/mol) of Zn2+ binding to the guanine-cytosine base pair. The present results show this procedure to be adequate for computations on the complexes of divalent cations with large oligonucleotides, which cannot be carried out by ab initio calculations.