Effects of confinement and crowding on folding of model proteins

TL;DR

This study uses molecular dynamics simulations to explore how confinement and crowding influence protein folding, revealing that confinement slightly slows folding and crowding can lead to aggregation depending on interaction strength.

Contribution

It provides new insights into the effects of confinement and crowding on protein folding dynamics using a coarse-grained simulation approach.

Findings

Confinement slightly slows folding but does not dramatically alter scenarios.

Crowding effects depend on inter-protein interactions, with attraction leading to aggregation.

Folding times are similar to single proteins when interactions are dominated by excluded volume.

Abstract

We perform molecular dynamics simulations for a simple coarse-grained model of crambin placed inside of a softly repulsive sphere of radius R. The confinement makes folding at the optimal temperature slower and affects the folding scenarios, but both effects are not dramatic. The influence of crowding on folding are studied by placing several identical proteins within the sphere, denaturing them, and then by monitoring refolding. If the interactions between the proteins are dominated by the excluded volume effects, the net folding times are essentially like for a single protein. An introduction of inter-proteinic attractive contacts hinders folding when the strength of the attraction exceeds about a half of the value of the strength of the single protein contacts. The bigger the strength of the attraction, the more likely is the occurrence of aggregation and misfolding.