STRUCTURAL ENERGETICS OF PROTEIN STABILITY AND FOLDING COOPERATIVITY

Numerous studies have demonstrated that the folding/unfolding transiti ons of globular proteins involve very few or no thermodynamically stab le intermediate structures between the folded and unfolded states. Rec ently we have developed a hierarchical partition function formalism ai med at gaining an understanding of the cooperative nature of thermal t ransitions in proteins. The energetic terms in the partition function are correlated to structural properties of the protein, namely buried surface areas and number of residues. Using phosphoglycerate kinase an d myoglobin as examples, it is shown that intermediately folded states are destabilized by two features: the unfavorable exposure of apolar surface area on regions of the intermediate structure remaining folded , and a decreased gain in configurational entropy for portions of the polypeptide chain which are adjacent to those regions remaining folded .