Conformational characteristics of the dimeric subunits of DNA from energy minimization studies. Mixed sugar-puckered dApdA, dApdT, dTpdA, and dTpdT.

An extensive investigation on the conformational characteristics of four deoxydinucleoside monophosphates, namely, dApdA, dApdT, dTpdA, and dTpdT was carried through calculation of the classical potential energy of the systems. The four major types of sugar-pucker sequences, namely, 3E-3E, 3E-2E, 2E-3E, 2E-2E, were included in the study. For each of the units, energies were computed for 96 starting conformations that resulted from the consideration of all possible low energy regions for the relevant seven dihedral angles and the four sugar-pucker sequences, and minimized by permitting all the seven dihedral angles to vary simultaneously. The number and the order of preference of low energy conformations obtained were found to be characteristic of the base sequence of the unit considered. The conformational states close to the A-DNA, B-DNA, C-DNA, and Watson-Crick DNA structures are noted to be preferred for all the units except dTpdT. The 3E-2E sugar-pucker sequence is the most favored and the 2E-3E sequence is the least favored state in terms of the associated number of local minima. For each unit, there exists a set of specific conformational states with more or less equal stabilities but different sugar-pucker sequences. The mixed sugar-pucker states 2E-3E and 3E-2E, when incorporated, in the conventional A-DNA and B-DNA conformational states, respectively, have energies that allow them to act as intermediates in the B form in equilibrium with A form transitions. Such transitions are most likely to occur at sites with a Thymine-Adenine base sequence. Available experimental results were interpreted in terms of their stabilities.