  A novel method combining the ensemble refinement by maximum entropy principle
and the force field fitting approach is presented. Its formulation allows to
continuously interpolate in between these two methods, which can thus be
interpreted as two limiting cases. A cross-validation procedure enables to
correctly assess the relative weight of both of them, distinguishing scenarios
where the combined approach is meaningful from those in which either ensemble
refinement or force field fitting separately prevails. The efficacy of their
combination is examined for a realistic case study of RNA oligomers. Within the
new scheme, molecular dynamics simulations are integrated with experimental
data provided by nuclear-magnetic-resonance measures. We show that force field
corrections are in general superior when applied to the appropriate force field
terms, but are automatically discarded by the method when applied to
inappropriate force field terms.
