Protein folding mediated by solvation: water expelling and formation of the hydrophobic core occurs after the structure collapse

TL;DR

This study proposes a protein folding mechanism where the structure forms prior to water expulsion from the hydrophobic core, integrating desolvation into the energy landscape theory and supported by experimental comparisons.

Contribution

It introduces a minimalist model demonstrating that protein structural formation occurs before water expulsion, offering a new perspective on the folding process.

Findings

Most structural formation occurs before water expulsion.

A near-native intermediate with a partially solvated core is observed.

Water is expelled in a final cooperative step after initial folding.

Abstract

The interplay between structure-search of the native structure and desolvation in protein folding has been explored using a minimalist model. These results support a folding mechanism where most of the structural formation of the protein is achieved before water is expelled from the hydrophobic core. This view integrates water expulsion effects into the funnel energy landscape theory of protein folding. Comparisons to experimental results are shown for the SH3 protein. After the folding transition, a near-native intermediate with partially solvated hydrophobic core is found. This transition is followed by a final step that cooperatively squeezes out water molecules from the partially hydrated protein core.