Molecular jamming - the cystine slipknot mechanical clamp in all-atom simulations

TL;DR

This study uses all-atom steered molecular dynamics to investigate the cystine slipknot mechanical clamp in proteins, revealing atomic-level details of its force resistance and jamming mechanism, and comparing it to shear-based mechanostability.

Contribution

It provides the first detailed atomic-level analysis of the cystine slipknot clamp's mechanics and compares it with shear-based protein stability models.

Findings

Cystine slipknot generates high stretching forces due to steric jamming.

Jamming is relieved by stepwise amino acid movement, with options for the initial amino acid.

Atomic detail clarifies differences between jamming and shear-based mechanostability.

Abstract

A recent survey of 17 134 proteins has identified a new class of proteins which are expected to yield stretching induced force-peaks in the range of 1 nN. Such high force peaks should be due to forcing of a slip-loop through a cystine ring, i.e. by generating a cystine slipknot. The survey has been performed in a simple coarse grained model. Here, we perform all-atom steered molecular dynamics simulations on 15 cystine knot proteins and determine their resistance to stretching. In agreement with previous studies within a coarse grained structure based model, the level of resistance is found to be substantially higher than in proteins in which the mechanical clamp operates through shear. The large stretching forces arise through formation of the cystine slipknot mechanical clamp and the resulting steric jamming. We elucidate the workings of such a clamp in an atomic detail. We also study the behavior of five top strength proteins with the shear-based mechanostability in which no jamming is involved. We show that in the atomic model, the jamming state is relieved by moving one amino acid at a time and there is a choice in the selection of the amino acid that advances the first. In contrast, the coarse grained model also allows for a simultaneous passage of two amino acids.