Molecular dynamics simulations of the anticodon hairpin of tRNA(Asp): Structuring effects of C-H center dot center dot center dot O hydrogen bonds and of long-range hydration forces

The inclusion of long-range solvent interactions out to 16 Angstrom in a molecular dynamics study of the anticodon loop of tRNA(Asp) led to an overall structural stabilization of the RNA hairpin tertiary interactions in a set of six independent fully solvated and neutralized 100 ps MD trajectories as compared to a shorter-ranged solvent interaction electrostatic model (8 Angstrom). The increased structural stabilization allowed for the emergence of non-classical C-H ... O hydrogen bonds in the MD trajectories. The presence of the C-H ... O hydrogen bonds in the crystal structure was subsequently verified and dynamically characterized and their contribution to the preservation of the tertiary native conformation was assessed. The MD trajectories generated using a truncation distance of 16 Angstrom for the electrostatic solute-solvent and solvent-solvent interactions, with no cutoffs applied to the electrostatic solute-solute interactions, compared to an earlier set of eight independent 100 ps MD trajectories using a smaller truncation distance of 8 Angstrom (Auffinger, P.; Louise-May, S.; Westhof, E. J. Am. Chem. Sec. 1995, 117, 6720-6726), revealed an increase in consistency of structural characteristics between individual MD trajectories of a given set and on average a decrease in root-mean-square deviation values from the starting crystal structure. Dihedral transitions in the sugar-phosphate backbone decreased and tertiary interactions specific to the loop topology were better preserved and showed reduced dynamical fluctuation. These results emphasize the important influence of long-ranged solvation forces on the stabilization of the tertiary structure of highly charged nucleic acid systems and signify that long-ranged theoretical models may be necessary for a truly accurate description of biomacromolecular solution structure and dynamics.