Molecular dynamics simulation of different helical forms of polyribocytidylic acid
Abstract
The polyribocytidylic acid (polyrC) is known to exist in different helical forms depending on the acidity of the environment. At neutral pH, the polyrC adopts a form of a single-stranded helix, under the acidic conditions (рН 3.5-5.7) formation of multistranded polyrC structures becomes possible due to the presence of hemiprotonated C+-C pairs, at pH < 3.5, the polyrC exists as a random coil. There is still an open discussion in the literature concerning the helical form of polyrC in the pH range 3.5 - 5.7. Some arguments indicate that the polyrC adopts a duplex form, others support the quadruplex hypothesis. In view of this, the investigation of polyrC helical forms is of particular interest. We carried out molecular dynamics simulations of different helical forms of polyrC: single-stranded helix r(C10), duplex [r(C10)]2, and two topologies 3'E and 5'E of polyrC quadruplex [r(C5)]4 (i-motif). The stable 5 ns trajectories were obtained for 3'E and 5'E topologies of polyrC i-motif [r(C5)]4. The hydrogen bonds between bases in C+-C pairs remained during all the trajectory time. Furthermore, in the structure of polyrC i-motif, hydrogen bonds, and water bridges, connecting strands of different duplexes were found. The characteristic of the i-motif CH---O hydrogen bonds across the narrow grooves were absent during the most part of the trajectory time. The investigated models of polyrC duplex [r(C10)]2 (helical rise = 3.11 Ao, helical twist = 300 and helical rise = 3.11 Ao, helical twist = 440 ) were found to be unstable and destroyed during the simulation. Based on the results of our calculations, we concluded that even if polyrC exists in a duplex form its structure should be substantially different from the models we have studied. The structure of single-stranded polyrC r(C10) underwent considerable changes in the course of simulation: the root-mean-square deviation with respect to the first trajectory frame was found to be ~ 5 Ao. A substantial disturbance of base stacking in the single-stranded polyrC was observed. Possibly this was caused by the presence of a lot of intramolecular hydrogen bonds seen in the structure of single-stranded polyrC in the molecular dynamics trajectory. During the molecular dynamics simulation, the sugar pucker transitions from C3'-endo to C2'-endo conformation were detected. In the case of polyrC quadruplex, the majority of sugars remained in the C3'-endo or C4'-Exo conformation, whereas in the case of single-stranded polyrC, almost all sugars adopted unusual to its C2'-endo form.
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