Role of hydration and intramolecular interactions in the helix-coil transition and helix-helix assembly in a deca-alanine peptide

TL;DR

This study investigates how hydration and intramolecular interactions influence the helix-coil transition and helix assembly in a deca-alanine peptide, highlighting the competing roles of hydration and intramolecular forces.

Contribution

It separates and analyzes short-range and long-range protein-solvent interactions, revealing their distinct impacts on peptide folding and assembly.

Findings

Hydration cavity contribution favors helix formation and assembly.

Short-range hydration interactions favor unfolded coil states.

Intramolecular interactions are crucial for helix stability and pairing.

Abstract

For a model deca-alanine peptide the cavity (ideal hydrophobic) contribution to hydration favors the helix state in the coil-to-helix transition and the paired helix bundle in the assembly of two helices. The energetic contributions of attractive protein-solvent interactions are separated into a short-range part arising from interactions with solvent in the first hydration shell and the remaining long-range part. In the helix-coil transition, short-range attractive protein-solvent interactions outweigh hydrophobic hydration and favor the unfolded coil states. Analysis of enthalpic effects shows that it is the favorable hydration of the peptide backbone that favors the unfolded state. Protein intramolecular interactions favor the helix state and are decisive in folding. In the pairing of two helices, the cavity contribution outweighs short-range attractive protein-water interactions. However, long-range, protein-solvent attractive interactions can either enhance or reverse this trend depending on the mutual orientation of the helices. In helix-helix assembly, change in enthalpy arising from change in attractive protein-solvent interactions favors disassembly. In helix pairing as well, favorable protein intramolecular interactions are found to be as important as hydration effects.