Some Problems of Computer Simulation of Non-Bonded Interactions in DNA

Abstract

Some difficulties in the application of various methods of computer modeling for the study of regularities of formation of spatial structure of DNA are analyzed. Computations of intermolecular interaction energy for all ten pairwise combinations of methylated bases (1-methylpyrimidines and 9-methylpurines) in various mutual base positions were performed due to the important role of nitrous bases. Local energy minima that correspond to different mutual positions of the molecules have been found using different molecular mechanics force fields, ab initio quantum mechanics, and density functional theory. The energy minima that correspond to three types of mutual molecule positions, namely, (1) base positions with two N–H…O and/or N–H…N hydrogen bonds; (2) nearly parallel arrangements of base ring planes, that is, base stacking; and (3) T-shaped (nearly perpendicular) base ring positions and hydrogen bond formation were extensively studied. The majority of these minima were obtained using methods of different complexities; however, the method of calculation determines which minimum is the deepest (global) for certain base combination and relative depths of various minima. Analysis of these simulations and of the computations on simple DNA fragments, as well as of extensive data from the literature suggests that there has been no method suitable for quantitative description of all the experimental data on non-bonded interactions in DNA. The comparison of energy and structure characteristics of the complexes calculated by various methods demonstrates their abilities and shortcomings. A valid description of non-bonded interactions of nucleic acids requires additional investigations of their simple fragments and the combined use of various methods.