Interdependence of conformational variables in double-helical DNA

Abstract

DNA exhibits conformational polymorphism, with the details depending on the sequence and its environment. To understand the mechanisms of conformational polymorphism and these transitions, we examine the interrelationships among the various conformational variables of DNA. In particular, we examine the stress-strain relation among conformational variables, describing base-pair morphology and their effects on the backbone conformation. For the calculation of base pairs, we use the method previously developed to calculate averages over conformational variables of DNA. Here we apply this method to calculate the Boltzmann averages of conformational variables for fixed values of one particular conformational variable, which reflects the strain in the structure responding to a particular driving stress. This averaging over all but one driving variable smooths the usual rough energy surface to permit observation of the effects of one conformational variable at a time. The stress-strain analyses of conformational variables of base pair slide, twist, and roll, which exhibit characteristic changes during the conformational transition of DNA, have shown that the conformational changes of base pairs are strongly correlated with one another. Furthermore, the stress-strain relations are not symmetrical with respect to these variables, i.e., the response of one coordinate to another is different from the reverse direction. We also examine the effect of conformational changes in base-pair variables on the sugar-backbone conformation by using the minimization method we developed. The conformational changes of base pairs affect the sugar pucker and other dihedral angles of the backbone of DNA, but each variable affects the sugar- backbone differently. In particular, twist is found to have the most influence in affecting the sugar pucker and backbone conformation. These calculated conformational changes in base pairs and backbone segments are consistent with experimental observations and serve to validate the calculation method.