van der Heijden, TWG, Read, DJ orcid.org/0000-0003-1194-9273, Harlen, OG orcid.org/0000-0002-4593-3547 et al. (3 more authors) (2020) Combined force-torque spectroscopy of proteins by means of multiscale molecular simulation. Biophysical Journal, 119 (11). pp. 2240-2250. ISSN 0006-3495
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. Both stretching and torsional forces are considered, and these may be applied independently of each other. As a proof of principle, we apply torsional forces to a coarse-grained continuum model of the antibody protein immunoglobulin G (IgG) using Fluctuating Finite Element Analysis and use it to 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. Zooming in, this part of the molecule is subjected to torques and stretching forces using molecular dynamics simulations on an atomistically resolved level, 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. From this, we assess how the measured twist-torque profiles develop with increasing stretching force, and show that they exhibit torsion stiffening, in qualitative agreement with experimental findings. We argue that combining the twist-torque profiles for various stretching forces effectively results in a combined force-torque spectroscopy analysis, which may serve as a mechanical signature for a biological macromolecule.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 Biophysical Society. This is an author produced version of an article published in Biophysical Journal. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Mathematics (Leeds) > Applied Mathematics (Leeds) The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Physics and Astronomy (Leeds) > Theoretical Physics (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 03 Nov 2020 15:18 |
Last Modified: | 13 Jan 2023 16:12 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.bpj.2020.09.039 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:167437 |
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Licence: CC-BY-NC-ND 4.0