  Recent computational efforts have shown that the current potential energy
models used in molecular dynamics are not accurate enough to describe the
conformational ensemble of RNA oligomers and suggest that molecular dynamics
should be complemented with experimental data. We here propose a scheme based
on the maximum entropy principle to combine simulations with bulk experiments.
In the proposed scheme the noise arising from both the measurements and the
forward models used to back calculate the experimental observables is
explicitly taken into account. The method is tested on RNA nucleosides and is
then used to construct chemically consistent corrections to the Amber RNA force
field that allow a large set of experimental data on nucleosides and
dinucleosides to be correctly reproduced. The transferability of these
corrections is assessed against independent data on tetranucleotides and
displays a previously unreported agreement with experiments. This procedure can
be applied to enforce multiple experimental data on multiple systems in a
self-consistent framework thus suggesting a new paradigm for force field
refinement.
