Solvent effects in the helix-coil transition model can explain the unusual biophysics of intrinsically disordered proteins.

We analyze a model statistical description of the polypeptide chain helix-coil transition, where we take into account the specificity of its primary sequence, as quantified by the phase space volume ratio of the number of all accessible states to the number corresponding to a helical conformation. The resulting transition phase diagram is then juxtaposed with the unusual behavior of the secondary structures in Intrinsically Disordered Proteins (IDPs) and a number of similarities are observed, even if the protein folding is a more complex transition than the helix-coil transition. In fact, the deficit in bulky and hydrophobic amino acids observed in IDPs, translated into larger values of phase space volume, allows us to locate the region in parameter space of the helix-coil transition that would correspond to the secondary structure transformations that are intrinsic to conformational transitions in IDPs and that is characterized by a modified phase diagram when compared to globular proteins. Here, we argue how the nature of this modified phase diagram, obtained from a model of the helix-coil transition in a solvent, would illuminate the turned-out response of IDPs to the changes in the environment conditions that follow straightforwardly from the re-entrant (cold denaturation) branch in their folding phase diagram.