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Changing the Mechanical Unfolding Pathway of FnIII(10) by Tuning the Pulling Strength

Mitternacht, Simon LU ; Luccioli, Stefano; Torcini, Alessandro; Imparato, Alberto and Irbäck, Anders LU (2009) In Biophysical Journal 96(2). p.429-441
Abstract
We investigate the mechanical unfolding of the tenth type III domain from fibronectin (FnIII(10)) both at constant force and at constant pulling velocity, by all-atom Monte Carlo simulations. We observe both apparent two-state unfolding and several unfolding pathways involving one of three major, mutually exclusive intermediate states. All three major intermediates lack two of seven native beta-strands, and share a quite similar extension. The unfolding behavior is found to depend strongly on the pulling conditions. In particular, we observe large variations in the relative frequencies of occurrence for the intermediates. At low constant force or low constant velocity, all three major intermediates occur with a significant frequency. At... (More)
We investigate the mechanical unfolding of the tenth type III domain from fibronectin (FnIII(10)) both at constant force and at constant pulling velocity, by all-atom Monte Carlo simulations. We observe both apparent two-state unfolding and several unfolding pathways involving one of three major, mutually exclusive intermediate states. All three major intermediates lack two of seven native beta-strands, and share a quite similar extension. The unfolding behavior is found to depend strongly on the pulling conditions. In particular, we observe large variations in the relative frequencies of occurrence for the intermediates. At low constant force or low constant velocity, all three major intermediates occur with a significant frequency. At high constant force or high constant velocity, one of them, with the N- and C-terminal beta-strands detached, dominates over the other two. Using the extended Jarzynski equality, we also estimate the equilibrium free-energy landscape, calculated as a function of chain extension. The application of a constant pulling force leads to a free-energy profile with three major local minima. Two of these correspond to the native and fully unfolded states, respectively, whereas the third one can be associated with the major unfolding intermediates. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biophysical Journal
volume
96
issue
2
pages
429 - 441
publisher
Cell Press
external identifiers
  • wos:000266377200015
  • scopus:58849130229
ISSN
1542-0086
DOI
10.1016/j.bpj.2008.09.043
language
English
LU publication?
yes
id
77417d45-9c1f-455e-9383-dac9d9d954ac (old id 1425400)
date added to LUP
2009-07-02 12:10:23
date last changed
2017-04-23 03:40:52
@article{77417d45-9c1f-455e-9383-dac9d9d954ac,
  abstract     = {We investigate the mechanical unfolding of the tenth type III domain from fibronectin (FnIII(10)) both at constant force and at constant pulling velocity, by all-atom Monte Carlo simulations. We observe both apparent two-state unfolding and several unfolding pathways involving one of three major, mutually exclusive intermediate states. All three major intermediates lack two of seven native beta-strands, and share a quite similar extension. The unfolding behavior is found to depend strongly on the pulling conditions. In particular, we observe large variations in the relative frequencies of occurrence for the intermediates. At low constant force or low constant velocity, all three major intermediates occur with a significant frequency. At high constant force or high constant velocity, one of them, with the N- and C-terminal beta-strands detached, dominates over the other two. Using the extended Jarzynski equality, we also estimate the equilibrium free-energy landscape, calculated as a function of chain extension. The application of a constant pulling force leads to a free-energy profile with three major local minima. Two of these correspond to the native and fully unfolded states, respectively, whereas the third one can be associated with the major unfolding intermediates.},
  author       = {Mitternacht, Simon and Luccioli, Stefano and Torcini, Alessandro and Imparato, Alberto and Irbäck, Anders},
  issn         = {1542-0086},
  language     = {eng},
  number       = {2},
  pages        = {429--441},
  publisher    = {Cell Press},
  series       = {Biophysical Journal},
  title        = {Changing the Mechanical Unfolding Pathway of FnIII(10) by Tuning the Pulling Strength},
  url          = {http://dx.doi.org/10.1016/j.bpj.2008.09.043},
  volume       = {96},
  year         = {2009},
}