Molecular Dynamics Simulations of the Anticodon Hairpin of tRNA(Asp) : Structuring Effects of C−H···O Hydrogen Bonds and of Long-Range Hydration Forces
Résumé
The inclusion of long-range solVent interactions out to 16 Å in a molecular dynamics study of the anticodon loop of tRNAAsp 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 Å). 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 Å 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 Å, 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