Solvent Effects in the Helix-Coil Transition Model can explain the Unusual Biophysics of Intrinsically Disordered Proteins

TL;DR

This paper models the helix-coil transition in polypeptides considering solvent effects and primary sequence specificity, explaining the unique biophysical behavior of Intrinsically Disordered Proteins (IDPs) through a modified phase diagram.

Contribution

It introduces a solvent-aware helix-coil transition model that accounts for IDPs' unique amino acid composition, linking phase diagram modifications to IDPs' environmental responsiveness.

Findings

IDPs have larger phase space volume due to amino acid composition.

The model's phase diagram explains IDPs' environmental sensitivity.

Modified phase diagram correlates with IDPs' conformational flexibility.

Abstract

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.