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Markov modeling of peptide folding in the presence of protein crowders

Nilsson, Daniel LU ; Mohanty, Sandipan LU and Irbäck, Anders LU (2018) In Journal of Chemical Physics 148(5).
Abstract

We use Markov state models (MSMs) to analyze the dynamics of a β-hairpin-forming peptide in Monte Carlo (MC) simulations with interacting protein crowders, for two different types of crowder proteins [bovine pancreatic trypsin inhibitor (BPTI) and GB1]. In these systems, at the temperature used, the peptide can be folded or unfolded and bound or unbound to crowder molecules. Four or five major free-energy minima can be identified. To estimate the dominant MC relaxation times of the peptide, we build MSMs using a range of different time resolutions or lag times. We show that stable relaxation-time estimates can be obtained from the MSM eigenfunctions through fits to autocorrelation data. The eigenfunctions remain sufficiently accurate to... (More)

We use Markov state models (MSMs) to analyze the dynamics of a β-hairpin-forming peptide in Monte Carlo (MC) simulations with interacting protein crowders, for two different types of crowder proteins [bovine pancreatic trypsin inhibitor (BPTI) and GB1]. In these systems, at the temperature used, the peptide can be folded or unfolded and bound or unbound to crowder molecules. Four or five major free-energy minima can be identified. To estimate the dominant MC relaxation times of the peptide, we build MSMs using a range of different time resolutions or lag times. We show that stable relaxation-time estimates can be obtained from the MSM eigenfunctions through fits to autocorrelation data. The eigenfunctions remain sufficiently accurate to permit stable relaxation-time estimation down to small lag times, at which point simple estimates based on the corresponding eigenvalues have large systematic uncertainties. The presence of the crowders has a stabilizing effect on the peptide, especially with BPTI crowders, which can be attributed to a reduced unfolding rate ku, while the folding rate kf is left largely unchanged.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Chemical Physics
volume
148
issue
5
publisher
American Institute of Physics
external identifiers
  • scopus:85041418662
ISSN
0021-9606
DOI
10.1063/1.5017031
language
English
LU publication?
yes
id
5a7bf6e8-6e8d-4069-9d98-5aa406427a47
date added to LUP
2018-02-15 12:30:16
date last changed
2018-11-21 21:38:03
@article{5a7bf6e8-6e8d-4069-9d98-5aa406427a47,
  abstract     = {<p>We use Markov state models (MSMs) to analyze the dynamics of a β-hairpin-forming peptide in Monte Carlo (MC) simulations with interacting protein crowders, for two different types of crowder proteins [bovine pancreatic trypsin inhibitor (BPTI) and GB1]. In these systems, at the temperature used, the peptide can be folded or unfolded and bound or unbound to crowder molecules. Four or five major free-energy minima can be identified. To estimate the dominant MC relaxation times of the peptide, we build MSMs using a range of different time resolutions or lag times. We show that stable relaxation-time estimates can be obtained from the MSM eigenfunctions through fits to autocorrelation data. The eigenfunctions remain sufficiently accurate to permit stable relaxation-time estimation down to small lag times, at which point simple estimates based on the corresponding eigenvalues have large systematic uncertainties. The presence of the crowders has a stabilizing effect on the peptide, especially with BPTI crowders, which can be attributed to a reduced unfolding rate k<sub>u</sub>, while the folding rate k<sub>f</sub> is left largely unchanged.</p>},
  articleno    = {055101},
  author       = {Nilsson, Daniel and Mohanty, Sandipan and Irbäck, Anders},
  issn         = {0021-9606},
  language     = {eng},
  month        = {02},
  number       = {5},
  publisher    = {American Institute of Physics},
  series       = {Journal of Chemical Physics},
  title        = {Markov modeling of peptide folding in the presence of protein crowders},
  url          = {http://dx.doi.org/10.1063/1.5017031},
  volume       = {148},
  year         = {2018},
}