Protein mechanical unfolding: importance of non-native interactions

TL;DR

This study uses all-atom molecular dynamics simulations to show that non-native interactions significantly influence the mechanical unfolding of a protein domain, revealing peaks in force-extension curves linked to breaking non-native hydrogen bonds.

Contribution

It demonstrates the crucial role of non-native interactions in protein unfolding, which are absent in simplified models, and predicts additional unfolding features for experimental validation.

Findings

Identification of a peak at 22 nm related to non-native hydrogen bonds

Prediction of an additional peak at 2 nm across multiple force fields

Non-native interactions are essential for accurate unfolding simulations

Abstract

Mechanical unfolding of the fourth domain of Distyostelium discoideum filamin (DDFLN4) was studied by all-atom molecular dynamics simulations, using the GROMOS96 force field 43a1 and the simple point charge explicit water solvent. Our study reveals an important role of non-native interactions in the unfolding process. Namely, the existence of a peak centered at the end-to-end extension 22 nm in the force-extension curve, is associated with breaking of non-native hydrogen bonds. Such a peak has been observed in experiments but not in Go models, where non-native interactions are neglected. We predict that an additional peak occurs at 2 nm using not only GROMOS96 force field 43a1 but also Amber 94 and OPLS force fields. This result would stimulate further experimental studies on elastic properties of DDFLN4.