Combined force-torque spectroscopy of proteins by means of multiscale molecular simulation

TL;DR

This paper introduces a multiscale simulation approach to analyze the mechanical properties of large proteins under combined force and torque, revealing torsion stiffening and potential for mechanical fingerprinting.

Contribution

It presents a novel multiscale method combining continuum and atomistic simulations to study protein mechanics under combined forces, advancing understanding of protein deformation behavior.

Findings

Identified the softest deformable region in IgG antibody.

Observed torsion stiffening with increasing stretching force.

Proposed combined force-torque profiles as mechanical signatures.

Abstract

Assessing the structural properties of large proteins is important to gain an understanding of their function in, e.g., biological systems or biomedical applications. We propose a method to examine the mechanical properties of proteins subject to applied forces by means of multiscale simulation. We consider both stretching and torsional forces, which can be applied independently of each other. We apply torsional forces to a coarse-grained continuum model of the antibody protein immunoglobulin G (IgG) using Fluctuating Finite Element Analysis and identify the area of strongest deformation. This region is essential to the torsional properties of the molecule as a whole, as it represents the softest, most deformable domain. We subject this part of the molecule to torques and stretching forces on an atomistic level, using molecular dynamics simulations, in order to investigate its torsional properties. We calculate the torsional resistance as a function of the rotation of the domain, while subjecting it to various stretching forces. We learn how these obtained torsion profiles evolve with increasing stretching force and show that they exhibit torsion stiffening, which is in qualitative agreement with experimental findings. We argue that combining the torsion profiles for various stretching forces effectively results in a combined force-torque spectroscopy analysis, which may serve as a mechanical signature for the examined molecule.