Hydrophobic and ionic-interactions in bulk and confined water with implications for collapse and folding of proteins

TL;DR

This study uses computer simulations to explore how hydrophobic and ionic interactions in water influence protein folding, especially in confined spaces like nanopores, revealing structural and interaction changes that affect folding stability.

Contribution

The paper provides new insights into water-mediated interactions and their impact on protein folding and stability in confined environments through detailed simulation analysis.

Findings

Collapse of hydrocarbon chains leads to ordered helical structures.

Hydrophobic and ionic interactions are significantly altered in nano confinement.

Ordered states of amphiphilic peptides are stabilized in cylindrical nanopores.

Abstract

Water and water-mediated interactions determine thermodynamic and kinetics of protein folding, protein aggregation and self-assembly in confined spaces. To obtain insights into the role of water in the context of folding problems, we describe computer simulations of a few related model systems. The dynamics of collapse of eicosane shows that upon expulsion of water the linear hydrocarbon chain adopts an ordered helical hairpin structure with 1.5 turns. The structure of dimer of eicosane molecules has two well ordered helical hairpins that are stacked perpendicular to each other. As a prelude to studying folding in confined spaces we used simulations to understand changes in hydrophobic and ionic interactions in nano droplets. Solvation of hydrophobic and charged species change drastically in nano water droplets. Hydrophobic species are localized at the boundary. The tendency of ions to be at the boundary where water density is low increases as the charge density decreases. Interaction between hydrophobic, polar, and charged residue are also profoundly altered in confined spaces. Using the results of computer simulations and accounting for loss of chain entropy upon confinement we argue and then demonstrate, using simulations in explicit water, that ordered states of generic amphiphilic peptide sequences should be stabilized in cylindrical nanopores.