Abstract
The conformational characteristics of the deoxydinucleoside monophosphates with adenine and thymine bases in all possible sequences, namely, dApdA, dApdT, dTpdA, and dTpdT have been studied using an improved set of energy parameters to calculate the total potential energy and an improved set of energy parameters to calculate the total potential energy and an improved version of the minimization technique to minimize the total energy by allowing all seven dihedral angles of the molecular fragment to vary simultaneously. The results reveal that the most preferred conformation in all these units usually corresponds to one of the four helical conformations, namely, the A‐DNA, B‐DNA, C‐DNA, and Watson‐Crick DNA models. These helical conformations differ in energies by about 3 kcal/mol with respect to one another. The conformations which could promote a loop or bend in the backbone are, in general, less stable by about 3.5 kcal/mol with respect to the respective lowest‐energy helical conformation. The results indicate that there is a definite influence of bases and their actual sequences on the preferred conformations of the deoxydinucleoside monophosphates. The lowest‐energy structure, although corresponding to one of the four helical conformations, differ with the type of the deoxydinucleoside monophosphate. Good or reasonable base stacking is noted in dApdA and dTpdA with both C(3′)‐endo and C(2′)‐endo sugars and in dApdT and dTpdT with only C(3′)‐endo sugar. The inversion of the base sequence in deoxydinucleoside monophosphates alters the order of preference of low‐energy conformations as well as the base‐stacking property of the unit. The paths linking the starting and final states in the (ω′, ω) plane show interesting features with regard to the energy spread, thus providing insight into the path of conformational movement ofthe molecule under slight perturbation. The stabilities of the A and B forms, including the internal energies of the C(3′)‐endo ans C(2′)‐endo sugar systems, indicate that for dTpdT the B → A transition is less probable. For dApdA, dApdT, and dTpdA this transition is probable in the same order of preference. We propose that the T‐A sequence in the polynucleotide chain might serve as the site accessible for B ⇄ A transitions. The theoretical predictions are in good agreement with the experimental observations.