Two-State Folding, Folding through Intermediates, and Metastability in a Minimalistic Hydrophobic-Polar Model for Proteins

TL;DR

This study uses a simplified hydrophobic-polar protein model with multicanonical Monte Carlo simulations to explore folding behaviors, revealing complex phenomena like two-state folding, intermediates, and metastability similar to real proteins.

Contribution

It demonstrates that even a minimalistic model can capture complex folding behaviors observed in real proteins through free-energy landscape analysis.

Findings

Identification of two-state folding behavior

Detection of folding through intermediates

Observation of glassy metastability

Abstract

Within the frame of an effective, coarse-grained hydrophobic-polar protein model, we employ multicanonical Monte Carlo simulations to investigate free-energy landscapes and folding channels of exemplified heteropolymer sequences, which are permutations of each other. Despite the simplicity of the model, the knowledge of the free-energy landscape in dependence of a suitable system order parameter enables us to reveal complex folding characteristics known from real bioproteins and synthetic peptides, such as two-state folding, folding through weakly stable intermediates, and glassy metastability.