Entropy and enthalpy of interaction between amino acid side chains in nanopores

TL;DR

This study uses molecular dynamics simulations to analyze how confinement in nanopores alters the thermodynamic interactions between amino acid side chains, impacting protein stability.

Contribution

It provides a detailed thermodynamic analysis of amino acid interactions in nanopores, revealing how confinement changes entropic and enthalpic contributions.

Findings

Hydrophobic interactions become enthalpically dominated under confinement.

Hydrogen bonding configurations differ in nanopores compared to bulk water.

Salt bridges are stabilized by entropy in nanopores.

Abstract

Understanding the stabilities of proteins in nanopores requires a quantitative description of confinement induced interactions between amino acid side chains. We use molecular dynamics simulations to study the nature of interactions between the side chain pairs ALA-PHE, SER-ASN and LYS-GLU in bulk water and in water-filled nanopores. The temperature dependence of the bulk solvent potentials of mean force and the interaction free energies in cylindrical and spherical nanopores is used to identify the corresponding entropic and enthalpic components. The entropically stabilized hydrophobic interaction between ALA and PHE in bulk water is enthalpically dominated upon confinement depending on the relative orientations between the side chains. In the case of SER-ASN, hydrogen bonded configurations that are similar in bulk water are thermodynamically distinct in a cylindrical pore, thus making rotamer distributions different from those in the bulk. Remarkably, salt bridge formation between LYS-GLU is stabilized by entropy in contrast to the bulk. Implications of our findings for confinement-induced alterations in protein stability are briefly outlined.