  The computational study of conformational transitions in nucleic acids still
faces many challenges. For example, in the case of single stranded RNA
tetranucleotides, agreement between simulations and experiments is not
satisfactory due to inaccuracies in the force fields commonly used in molecular
dynamics simulations. We here use experimental data collected from
high-resolution X-ray structures to attempt an improvement of the latest
version of the AMBER force field. A modified metadynamics algorithm is used to
calculate correcting potentials designed to enforce experimental distributions
of backbone torsion angles. Replica-exchange simulations of tetranucleotides
including these correcting potentials show significantly better agreement with
independent solution experiments for the oligonucleotides containing pyrimidine
bases. Although the proposed corrections do not seem to be portable to generic
RNA systems, the simulations revealed the importance of the alpha and beta
backbone angles on the modulation of the RNA conformational ensemble. The
correction protocol presented here suggests a systematic procedure for
force-field refinement.
