Chemical probing experiments such as SHAPE are routinely
used to
probe RNA molecules. In this work, we use atomistic molecular dynamics
simulations to test the hypothesis that binding of RNA with SHAPE
reagents is affected by cooperative effects leading to an observed
reactivity that is dependent on the reagent concentration. We develop
a general technique that enables the calculation of the affinity for
arbitrary molecules as a function of their concentration in the grand-canonical
ensemble. Our simulations of an RNA structural motif suggest that,
at the concentration typically used in SHAPE experiments, cooperative
binding would lead to a measurable concentration-dependent reactivity.
We also provide a qualitative validation of this statement by analyzing
a new set of experiments collected at different reagent concentrations.