Dependence of A-RNA simulations on the choice of the force field and salt strength

We present an extensive molecular dynamics study (0.6 μs in total) on three A-RNA duplexes. The dependence of the A-RNA geometry on force fields (Parm99 and Parmbsc0) and salt strength conditions (∼0.18 M net-neutralizing Na+ and ∼0.3 M KCl) was investigated. The Parmbsc0 force field makes the A-RNA duplex more compact in comparison to the Parm99 by preventing temporary α/γ t/t flips common in Parm99 simulations. Nevertheless, since the α/γ t/t sub-state occurs to certain extent in experimental A-RNA structures, we consider both force fields as viable. The stabilization of the A-RNA helices caused by the Parmbsc0 force field includes visible reduction of the major groove width, increase of the base pair roll, larger helical inclination and small increases of twist. Therefore, the Parmbsc0 shifts the simulated duplexes more deeply into the A-form. Further narrowing of the deep major groove is observed in excess salt simulations, again accompanied by larger roll, inclination and twist. The cumulative difference between Parm99/lower-salt and Parmbsc0/higher-salt simulations is ∼4–8 Å for the average P⋯P distances, and −0.7 to −2.5°, −2.0 to −5.4°, −2.6 to −8.6° and 1.7 to 7.0° for the twist, roll, inclination and propeller, respectively. The effects of the force field and salt condition are sequence-dependent. Thus, the compactness of A-RNA is sensitive to the sequence and the salt strength which may, for example, modulate the end-to-end distance of the A-RNA helix. The simulations neatly reproduce the known base pair roll re-distribution in alternating purine-pyrimidine A-RNA helices.