Assumptions made to address some of these problems: Replace ag with AE-assume that the large entropic contributions to protein folding mostly cancel when considering the folding of different sequences to a similar structure 2. Model ae using molecular mechanics energy functions -do not include explicit solvent but instead use approximate empirical functions 3. Assume that there are no specific interactions between residues in the unfolded state Corollary: the energy of the unfolded states depends oNly on the amino acid composition of the proteinAssumptions made to address some of these problems: 1. Replace ∆G with ∆E - assume that the large entropic contributions to protein folding mostly cancel when considering the folding of different sequences to a similar structure. 2. Model ∆E using molecular mechanics energy functions - do not include explicit solvent but instead use approximate empirical functions. 3. Assume that there are no specific interactions between residues in the unfolded state. Corollary: the energy of the unfolded states depends ONLY on the amino acid composition of the protein