Molecular Dynamics Simulation of Folding and Diffusion of Proteins in Nanopores

TL;DR

This study uses advanced molecular dynamics simulations to explore how proteins fold and diffuse within nanopores, revealing how pore size, temperature, and wall interactions influence protein behavior and transport efficiency.

Contribution

It introduces a novel simulation approach combining discontinuous molecular dynamics and Langevin dynamics to study protein folding and diffusion in nanopores.

Findings

Proteins exhibit folding/unfolding transitions near the folding temperature in attractive pores.

Protein diffusivity depends on temperature, pore size, and interaction potentials.

Transport can be faster in smaller pores under certain conditions.

Abstract

A novel combination of discontinuous molecular dynamics and the Langevin equation, together with an intermediate-resolution model, are used to carry out long (several $\mu$s) simulation and study folding transition and transport of proteins in slit nanopores. Both attractive ($U^+$) and repulsive ($U^-$) interaction potentials between the proteins and the pore walls are considered. Near the folding temperature $T_f$ and in the presence of $U^+$ the proteins undergo a repeating sequence of folding/partially-folding/ unfolding transitions, while $T_f$ decreases with decreasing pore sizes. The opposite is true when $U^-$ is present. The proteins' effective diffusivity $D$ is computed as a function of their length (number of the amino acid groups), temperature $T$, the pore size, and the interaction potentials $U^\pm$. Far from $T_f$, $D$ increases (roughly) linearly with $T$, but due to the thermal fluctuations and their effect on the proteins' structure near $T_f$, the dependence of $D$ on $T$ in this region is nonlinear. Under certain conditions, transport of proteins in smaller pores can be {\it faster} than that in larger pores.