Developing a Minimal Model for the Coil-Helix Transition

Folding from a coil conformation to a helix conformation occurs via a cooperative pathway: the formation of the first helical monomer is unfavorable but subsequent neighboring monomers transition into the helical state more easily. Herein, we introduce a minimal, highly tunable coarse-grained one-bead-per-residue model that reproduces this behavior and enables quantitative comparison with the Zimm–Bragg theory. From simulations we extract the propagation and nucleation parameters (s, σ), thereby quantifying helical propensity and cooperativity. We vary the spacing between hydrogen bonding monomers (i → i + m motif with m = 3, 4, 5, 6 corresponding to 3₁₀, α, π and "1-7" helices) and how this spacing affects various parameters such as the persistence length, projection length and the cooperativity parameter. Our findings hint at why helices with more than 4 residues monomers between hydrogen bonded ones, such as π-helices, are scarcely observed in nature, and why 3₁₀-helices are more likely to be observed as transient intermediates in the helix formation pathway.