A study on local-global cooperativity in protein collapse

We study the effect of secondary structure formation on cooperativity of pr otein collapse using a simple homopolymer model on a "210" lattice that all ows a geometrically consistent representation of alpha-helical conformation . Monte carlo simulations were carried out in the range of temperatures and energetic parameters that characterize relative strength of global (i.e., between monomers that are far apart in sequence) and local (helix-stabilizi ng) contacts R = eta(g)/eta(1). The complete phase diagram presented here e xhibits a narrow region of temperatures and R-values in which compact confo rmations with considerable helical content dominate the equilibrium. It was shown that at certain values of R, the collapse transition occurs in a nar row temperature range and is accompanied by a pronounced increase of helica l content. However, the simulations do not support a two-state transition s cenario at which transition occurs between two (metha) stable states corres ponding to free energy minima. Rather, we observe at all temperatures and a ll values of R a single stable state that evolves, as temperature gets lowe r, toward more compact conformations. We argue that additional factors such as sequence specificity and/or side-chain packing should be taken into acc ount to explain the two-state character of folding transition observed in r eal proteins.