LOCAL CONFORMATIONAL SIGNALS AND THE STATISTICAL THERMODYNAMICS OF COLLAPSED HELICAL PROTEINS

We investigate the role that local conformational tendencies can have in guiding the folding of helical proteins, using simple statistical m echanical models. The theory provides a synthesis of classical models of the helix-coil transition in polymers with an approximate treatment of the effects of excluded volume, confinement, and packing alignment of the helices based on a free energy function. The theory studies th e consequences of signals encoded locally in the sequence as stabiliza tion energies associated with three types of local structure: native h elical conformations, native non-helical conformations, and native hel ix caps or start-stop signals. The role of randomness in the energies of conformations due to tertiary interactions is also studied vis-ii-v is the difficulty of conformational search. The thermal behavior of th e model is presented for realistic values of the conformational signal energies, which can be estimated from experimental studies on peptide fragments. Estimates are made for the relative contribution of local signals and specific tertiary interactions to the folding stability ga p. (C) 1996 Academic Press Limited