Hoogsteen and stacked structures of the 9-methyladenine center dot center dot center dot 1-methylthymine pair are populated equally at experimental conditions: Ab initio and molecular dynamics study

The potential energy surface (PES) of the 9-methyladenine...1-methylthymine (mA...mT) nucleic acid base pair was investigated using molecular dynamics /quenching method utilizing the Cornell et al. (Cornell, W. D.; Cieplak, P. : Bayly, C. I.: Gould, I. R., Merz, K. M., Jr.; Ferguson, D. M.; Spellmeyer , D. C.; Fox, T.; Caldwell, J. W.; Kollman, P. A. J. Am. Chem. Sec. 1995, 1 17, 5179) empirical force field. Altogether 16 energy minima were found, 4 of them were planar, hydrogen-bonded, and 9 stacked. The accuracy of the st abilization energies evaluated with Cornell et al. empirical force field wa s verified by comparing them with correlated ab initio stabilization energi es and good agreement was found for hydrogen-bonded as well as stacked pair s. NVE and NVT free energy surfaces were estimated by means of computer sim ulations. In the NVE simulations stacked structures prevail, while in the N VT calculations an equal mixture of planar hydrogen bonded reversed Hoogste en and Hoogsteen structures, and two stacked structures was found. The aver aged stabilization enthalpy considering all the dimer structures (NVT simul ations) is ii kcal/mol and agrees well with the experimental stabilization enthalpy for the formation of mA mT pair (13 kcal/mol) obtained from field ionization mass spectrometry measurements at conditions comparable to the N VT simulations.