DFT study of DNA sequence dependence at the level of dinucleoside monophosphates

In this work we search for new energy minima of desoxydinucleoside monophosphate complexes with Na-ions (dDMPs) as the minimal fragments of DNA single strand via Density Functional Theory (DFT) computations and summarize our previous findings in this field. The analysis is illustrated by graphs of distribution of sugar-phosphate and glycosyl torsions as well as of sugar puckering for energy minima of various base sequences to elucidate the contributions of intra-strand interactions to DNA structure and polymorphism. Our recent computations revealed that the characteristic features of BI, BII, and AI families of DNA duplex conformations are initially predisposed in the dDMPs and namely in their local energy minima. New calculations and the analysis of our previous results enable us to verify and to draw conclusions about important role of sugar-phosphate backbone in the formation and sequence dependence of DNA duplexes. The optimized conformations of dDMPs with purine-purine and purine-pyrimidine sequences are characterized by substantial superposition of base rings whereas those with pyrimidine-pyrimidine and pyrimidine-purine sequences have small if any superposition. This result reveals itself as a universal rule for energy minima corresponding to all four families of right-handed duplexes with Watson-Crick base pairs (BI, BII, AI and AII). The character of base-base overlap is independent of the degree of variation of each of the backbone torsions, which may vary substantially or only slightly with the nucleoside sequence within a family. Computations on dDMP structures corresponding to duplexes with Hoogsteen pairs, started from the torsion angle values of the duplex, located characteristic energy minima for dApdT and dTpdA representative of this conformation. We observe that the rule of sequence dependence of base superposition does not apply to these systems. Biological consequences of existence of the obtained minima and the implications of the revealed regularities are discussed.