Peierls-Nabarro Barrier and Protein Loop Propagation

TL;DR

This study models protein loop propagation as a kink moving along the backbone lattice, analyzing energy barriers and dissipative forces that influence folding dynamics using coarse-grained molecular dynamics.

Contribution

It introduces a novel approach to understanding protein folding by modeling loop propagation as a kink in a discrete nonlinear Schrödinger equation framework.

Findings

Energy barriers significantly affect kink propagation in proteins.

Dissipative forces influence the folding pathway and native state attainment.

Kink dynamics can predict stress and relief regions in protein structures.

Abstract

When a self-localized quasiparticle excitation propagates along a discrete one dimensional lattice, it becomes subject to a dissipation that converts the kinetic energy into lattice vibrations. Eventually the kinetic energy does no longer enable the excitation to cross over the minimum energy barrier between neighboring sites, and the excitation becomes localized within a lattice cell. In the case of a protein, the lattice structure consists of the C-alpha backbone. The self-localized quasiparticle excitation is the elemental building block of loops. It can be modeled by a kink which solves a variant of the discrete non-linear Schroedinger equation (DNLS). We study the propagation of such a kink in the case of protein G related albumin-binding domain, using the UNRES coarse-grained molecular dynamics force field. We estimate the height of the energy barriers the kink needs to cross over, in order to propagate along the backbone lattice. We analyse how these barriers gives rise to both stresses and reliefs which control the kink movement. For this, we deform a natively folded protein structure by parallel translating the kink along the backbone away from its native position. We release the transposed kink, and we follow how it propagates along the backbone towards the native location. We observe that the dissipative forces which are exerted on the kink by the various energy barriers, have a pivotal role in determining how a protein folds towards its native state.