| Biomolecule’s function is determined by their structure,and RNA’s function is closely related to conformational dynamics of base pairs.For example,RNA folding involves dynamic formation and removal of the base pairing,and there is a certain dynamics for the base pair during post-transcriptional modification.Riboswitch frequently has extremely dynamic structures of base pairs when it functions.Thus,it is essential to research base pair structural dynamics in RNA to comprehend how RNA works.Molecular dynamics simulation is the method to study the RNA structure in solution.However,more research is required to determine the reliability of MD modeling.We thoroughly investigated the water model and force field of the MD simulation.On the one hand,we examined six force fields using two hairpin RNAs.We discovered that LJbb and OL3 were the two force fields with the best performance through the statistical distribution of conformational characteristics after simulations,including the distribution of hydrogen bonds in the apical loop region,G17 glycoside angle,backbone conformation,and sugar conformation in the apical loop region.On the other hand,we also assessed eight water models using these two hairpin RNAs.We also examined the structural traits of the same four features and contrasted them with the findings of the experiment.The final data demonstrate that the three best water models are SPC/E,SPC/E_b,and TIP3P.These two force fields and three water models can be used later when simulating comparable systems.This research is crucial for the optimization of simulation parameters.After establishing the appropriate simulation parameters,we will investigate the structural dynamics of RNA base pairs.First,we separated the base pairs into various regions according to their positions.Then,a series of hairpin RNAs containing these base pairs were designed respectively,and they were simulated for the same duration with the same settings.Finally,we extracted dihedral angles from the simulation trajectories for principal component analysis,revealing the structural characteristics of base pairs.For the base pairs in the double helix region,we found that different neighboring base pairs had no obvious effect on the structure of the central base pair.For the base pairs adjacent to the apical loop,there are position-dependent structural dynamics,and the structure of 3′residue has more different conformations.This structural difference is reduced when we replace the apical loop with GNRA.For terminal base pairs,due to the particularity of their positions,the residues at two positions are more dynamic than those in the double helix region.Further analysis shows that the residues at the 5′end are more dynamic than those at the 3′end.In addition,we also found that the structural dynamics of the terminal base pair will be transferred to the second base pair,while the structure of the third base pair has very little dynamics.For the base pairs close to the bulge,we also found position-dependent structural dynamics.The structure of the residue close to the bulge residue will be very dynamic.When the bulge residue turns inward to form hydrogen bonds with the surrounding residues,the conformation of the residue at this position is most similar to that of the double helix region.For the base pairs close to the internal loop,the conformation is relatively stable,which is very similar to the base pair structure of the double helix region.To sum up,our research is of great significance for the prediction and optimization of RNA structure and the understanding how RNA functions. |
