Palamarchuk G. "Conformational characteristics and intramolecular hydrogen bonds in 2'-deoxyribonucleotides and their protonated tautomers"

The object of the research is: protonation of heteroatoms of nucleobases of anions of the canonical 2'-deoxyribonucleotides and their influence to the conformational characteristics of nucleotides and parameters of intramolecular hydrogen bonds. The purpose of the research is: definition of the conformational characteristics and intramolecular hydrogen bonds in monoanions of canonical 2'-deoxyribonucleotides and their protonated by heteroatoms of nucleobases tautomers. Special attention was handling to the influence of the intramolecular hydrogen bonds to the conformation and relative energy of molecule. The methods employed are: theoretical methods of non-empiric quantum chemistry using the density functional theory with the Becke's three-parameter exchange functional and the gradient-corrected functional of Lee, Yang and Parr (6-311++G(d,p) and aug-cc-pvdz basis sets were applied) and at the МР2/6-311G(d,p) level of theory. Intramolecular interactions was carried out within Bader's AIM approach using the B3LYP/6-31++G(d,p) wave function and Natural Bonding Orbitals Theory (NBO). The molecular dynamics simulations of AMP molecule were carried out using Car-Parrinello molecular dynamics (CPMD) simulations. The theoretical and practical value of the research: systematical investigation of conformational and energetical characteristics of anions of the canonical 2'-deoxyribonucleotides was performed; set of intramolecular hydrogen bonds that influence to the geometry of nucleotides was shown; changes in energetical characteristics of molecules and in characters of intramolecular interactions in anions of canonical 2'-deoxyribonucleotides during their incorporation to the structure of DNA was analyzed; influence of protonation of heteroatoms of nucleobases to the structure, energetical characteristics and intramolecular interactions in anions of the canonical 2'-deoxyribonucleotides was studied; value of proton affinity for each of the heteroatoms of nucleobases and the distribution of protonated tautomers was defined; for the AMP molecule mutual influence of conformational dynamics of nucleotides and their tautomerical transition was described. The novelty: obtained data are the base for the parameterization of force fields of classical molecular dynamics, that used for modeling of structure and dynamics of DNA. Information about characters of changes of conformational characteristics of the nucleotides during the protonation is useful for understanding of molecular mechanisms of damages of nucleic acids structure due to the action of acid agents. Implantation: none. Region of application: parametrization of force fields of classic molecular dinamics, modeling of structure and dinamics of the DNA by the methods of classic molecular dynamics.