Modeling the experimental ensemble also requires representing the chemical compositional heterogeneity. This heterogeneity can result from covalent modification (e.g. post-translational modification) or the presence of a binding partner stabilized by non-covalent interactions (e.g. a subunit of a macromolecular complex, a small molecule ligand, or even a solvent molecule). Using ensemble-based approaches leads to the same model size selection problems outlined above. Refining the weight of different conformational ensemble members in the modified/bound state also connects this heterogeneity more naturally to the multiconformer format. A major issue for encoding compositional heterogeneity in multiconformer models is that the current formats use the exact same representation for conformational and compositional heterogeneity, creating ambiguity about the various states present in the models and their relationship to the experimental ensemble.