Simulations of A-RNA Duplexes. The Effect of Sequence, Solute Force Field, Water Model, and Salt Concentration

We have carried out an extended reference set of explicit solvent molecular dynamics simulations (63 simulations with 8.4 mu s of simulation data) of canonical A-RNA duplexes. Most of the simulations were done using the latest variant of the Cornell et al. AMBER RNA force field bsc0 chi(OL3), while several other RNA force fields have been tested. The calculations show that the A-RNA helix compactness, described mainly by geometrical parameters inclination, base pair roll, and helical rise, is sequence-dependent. In the calculated set of structures, the inclination varies from 10 degrees to 24 degrees. On the basis of simulations with modified bases (inosine and 2,6-diaminopurine), we suggest that the sequence-dependence of purely canonical A-RNA double helix is caused by the steric shape of the base pairs, i.e., the van der Waals interactions. The electrostatic part of stacking does not appear to affect the A-RNA shape. Especially visible is the role of the minor groove amino group of purines. This resembles the so-called Dickerson-Calladine mechanical rules suggested three decades ago for the DNA double helices. We did not identify any long-living backbone substate in A-RNA double helices that would resemble, for example, the B-DNA BI/BII dynamics. The variability of the A-RNA compactness is due to mutual movements of the consecutive base pairs coupled with modest change of the glycosidic chi torsion. The simulations further show that the A-RNA compactness is modestly affected by the water model used, while the effect of ionic conditions, investigated in the range from net-neutral condition to similar to 0.8 M monovalent ion excess salt, is smaller.