A thermodynamic model for the helix-coil transition coupled to dimerization of short coiled-coil peptides.

A simple thermodynamic formalism is presented to model the conformational transition between a random-coil monomeric peptide and a coiled-coil helical dimer. The coiled-coil helical dimer is the structure of a class of proteins also called leucine zipper, which has been studied intensively in recent years. Our model, which is appropriate particularly for short peptides, is an alternative to the theory developed by Skolnick and Holtzer. Using the present formalism, we discuss the multi-equilibriatory nature of this transition and provide an explanation for the apparent two-state behavior of coiled-coil formation when the helix-coil transition is coupled to dimerization. It is found that such coupling between multi-equilibria and a true two-state transition can simplify the data analysis, but care must be taken in using the overall association constant to determine helix propensities (w) of single residues. Successful use of the two-state model does not imply that the helix-coil transition is all-or-none. The all-or-none assumption can provide good numerical estimates when w is around unity (0.35 < or = w < or = 1.35), but when w is small (w < 0.01), similar estimations can lead to large errors. The theory of the helix-coil transition in denaturation experiments is also discussed.