Concretely, for example, consider a situation where a minor rotameric state for a particular sidechain ought to be slightly populated in the bound state at equilibrium and becomes dominant in the unbound state. If the actual sampling of the bound state misses that minor conformer entirely and switching to the unbound state is so rapid as to miss rotameric transitions, there is a high likelihood that resulting free energy estimates will be biased (unless sampling of reverse transformations is somehow sufficient to recover). Here, then, we find it helpful to assess dihedral sampling in the end states and assess whether switching transitions ever sample rotamers appropriate for their target end state.