Is the molten globule a third phase of proteins?

The equilibrium properties of proteins are studied by Monte Carlo simulation of two simplified models of protein-like heteropolymers. These models emphasize the polymeric entropy of the fluctuating polypeptide chain. Our calculations suggest a generic phase diagram that contains a thermodynamically distinct "molten globule" state in addition to a rigid native state and a nontrivial unfolded state. The roles of side-chain packing and loop entropy are discussed.