Effects of confinement on thermal stability and folding kinetics in a simple Ising-like model

TL;DR

This study uses a generalized Ising-like model to analyze how confinement between walls affects protein stability and folding kinetics, revealing two regimes where confinement either stabilizes or destabilizes the folded state.

Contribution

It introduces a modified Wako-Saito-Munoz-Eaton model to systematically investigate confinement effects on protein folding across different structures.

Findings

Confinement enhances stability at larger wall distances.

Reduced wall distance decreases folding temperature and rate.

Folding parameters scale with wall distance as R-γ, with γ between 1.42 and 2.35.

Abstract

In cellular environment, confinement and macromulecular crowding play an important role on thermal stability and folding kinetics of a protein. We have resorted to a generalized version of the Wako-Saito-Munoz-Eaton model for protein folding to study the behavior of six different protein structures confined between two walls. Changing the distance 2R between the walls, we found, in accordance with previous studies, two confinement regimes: starting from large R and decreasing R, confinement first enhances the stability of the folded state as long as this is compact and until a given value of R; then a further decrease of R leads to a decrease of folding temperature and folding rate. We found that in the low confinement regime both unfolding temperatures and logarithm of folding rates scale as R-{\gamma} where {\gamma} values lie in between 1.42 and 2.35.