To compute the free energy change associated with molecular folding, the conformational states (i.e., "folded" and "unfolded") must first be given definitions by the researcher performing the calculation. If most conformational states are very clearly either folded or unfolded, i.e., in the case of a strongly cooperative foldamer with a single folded state, the free energy difference between them will be relatively insensitive to the precise definitions of the folded and unfolded states. However, if there is a not a clear division between the folded and unfolded states, different definitions of the conformational states may dramatically affect the results of the free energy calculation.