Published October 22, 2021 | Version v1
Journal article Open

Interpretation of Single-Molecule Force Experiments on Proteins Using Normal Mode Analysis

  • 1. Institute of Molecular Biology, Slovak Academy of Sciences, Dúbravská cesta 21, 845 51 Bratislava, Slovakia
  • 2. Center for Interdisciplinary Biosciences, P. J. Šafárik University, Technology and Innovation Park, Trieda SNP 1, 041 54 Košice, Slovakia

Description

Single-molecule force spectroscopy experiments allow protein folding and unfolding to be explored using mechanical force. Probably the most informative technique for interpreting the results of these experiments at the structural level makes use of steered molecular dynamics (MD) simulations, which can explicitly model the protein under load. Unfortunately, this technique is computationally expensive for many of the most interesting biological molecules. Here, we find that normal mode analysis (NMA), a significantly cheaper technique from a computational perspective, allows at least some of the insights provided by MD simulation to be gathered. We apply this technique to three non-homologous proteins that were previously studied by force spectroscopy: T4 lysozyme (T4L), Hsp70 and the glucocorticoid receptor domain (GCR). The NMA results for T4L and Hsp70 are compared with steered MD simulations conducted previously, and we find that we can recover the main results. For the GCR, which did not undergo MD simulation, our approach identifies substructures that correlate with experimentally identified unfolding intermediates. Overall, we find that NMA can make a valuable addition to the analysis toolkit for the structural analysis of single-molecule force experiments on proteins.

Notes

This research was supported by VEGA 1/0175/19 and 2/0131/20; APVV-18-0285; BioPickmol; ITMS2014+: 313011AUW6; and the Integrated Infrastructure Operational Programme; and also received funding from the ERDF and Interreg SK-AT StruBioMol ITMS: 305011 × 666

Files

2021_Bauer_Nanomaterials.pdf

Files (5.0 MB)

Name Size Download all
md5:5bb16cff583557650966cbfdd76fdba7
5.0 MB Preview Download

Additional details

Funding

European Commission
CasProt - Fostering high scientific quality in protein research in Eastern Slovakia 952333

References

  • ACS style guide