At some level, of course, charges ought to be conformer-dependent in the sense that the underlying electronic structure of a molecule depends on its conformer. However, this electronic structure is not possible to treat within a classical fixed-charge model, as charges would need to rearrange with the molecule and this rearrangement would need its energetics modeled -necessitating the use of a Hamiltonian to describe these charge fluctuations (such as a polarizable or fluctuating charge model ). Within the classical fixed-charge framework, then, the solution is to use a single set of fixed-charges -often, a set derived from an optimal or representative conformer, or one obtained from averaging across conformers.