A HETEROPOLYMER MODEL STUDY FOR THE MECHANISM OF PROTEIN-FOLDING

A heteropolymer model of randomly self-interacting chains in two dimen sions is studied with numerical simulations in order to elucidate the folding mechanism of protein. We find that the model occasionally show s folding propensity depending on the sequence of random numbers given to the chain. We study the thermodynamic and kinematic roles in the f olding mechanism by grouping the local energy minima found in the simu lations into clusters according to the similarity of their conformatio ns. It is suggested that the local minima to which some heteropolymers show a folding tendency are always the lowest energy states of the en ergy spectrum within a cluster, though which cluster is selected depen ds on the sequence. For the eight random sequences we study, we find t hat the energy gap between the ground stale and excited states is litt le correlated with folding or nonfolding. We rather find that folding propensities are correlated with the global structure of the average e nergy surface, implying a dominant kinetic role in the folding mechani sm, although thermal factors cannot be ignored as the mechanism of cho osing the ground state within a cluster of states connected by small d eformations. We suggest that a hierarchical cluster structure plays an important role in selecting a unique folded state out of the huge num ber of local minima of heteropolymers. (C) 1997 John Wiley & Sons, Inc .