CELL-DYNAMICS OF FOLDING IN 2-DIMENSIONAL MODEL PROTEINS

Background: Functionally useful proteins are sequences of amino acids that fold rapidly under appropriate conditions into their native state s. It is believed that rapid folders are sequences for which the foldi ng dynamics entail the exploration of restricted conformations - the p hase space can be thought of as a folding funnel. While there are many experimentally accessible predictions pertaining to the existence of such funnels and a coherent picture of the kinetics of folding has beg un to emerge, there have been relatively few simple studies in the con trolled setting of well-characterized lattice models. Results: We desi gn rapidly folding sequences by assigning the strongest couplings to t he contacts present in a target native state in a two-dimensional mode l of heteropolymers. Such sequences have large folding transition temp eratures and low grass transition temperatures. The dependence of medi an folding times on temperature is investigated. The pathways to foldi ng and their dependence on the temperature are illustrated via a study of the cell dynamics - a mapping of the dynamics into motion within t he space of the maximally compact cells.Conclusions: Folding funnels c an be defined operationally in a coarse-grained sense by mapping the s tates of the system into maximally compact conformations and then by i dentifying significant connectivities between them.