DEVELOPMENT OF SIMULATION-MODELS FOR PROTEIN-FOLDING IN A THERMAL ANNEALING PROCESS .1. A SIMULATION OF BPTI FOLDING BY THE PEARL NECKLACE MODEL

A model system is proposed to simulate the folding processes of protei ns during thermal annealing. This system consists of four subsystems: (i) the pearl necklace model with isotropic inter-residue interactions ; (ii) the extended pearl necklace model with anisotropic interaction potentials; (iii) molten globule phase dynamics; and (iv) final genera tion of the three-dimensional structure of a given protein. In this pa per results obtained with the pearl necklace model are reported. This model consists of spherical elements and virtual bonds of 3.8 angstrom in length and is intended to simulate dynamical processes at relative ly high temperature where entropic terms play a dominant role. Inter-r esidue interactions are composed of spherical soft repulsive potential s and hydrophobic interactions inherent to respective residues. A simu lation of folding processes of BPTI starting from the fully extended c onformation indicated that intermediates, even at early stages of fold ing, are not randomly coiled but assume organized structures that rese mble, to some extent, the native conformation.