ON LEVINTHAL PARADOX AND THE THEORY OF PROTEIN-FOLDING

A general model of protein folding is proposed that links together con cepts from molecular physics, thermodynamics and chemical kinetics. Th e model is based on a description of the potential hypersurface throug h a three-level taxonomy: conformational substates, conformational sta tes, and free-energy levels. The required parameters are either estima ted or taken from experimental or computational literature data. The f ree-energy barriers between conformational states are shown to be esse ntially negentropic in the folding direction. A consistent picture eme rges, which answers Levinthal's paradox. It consists in a biased rando m walk with a very high degree of percolation. Finally, the model lead s to a sketch of a possible algorithm for an ab initio simulation of p rotein folding. (C) 1998 Elsevier Science B.V.