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Molecular Dynamics Simulations of Intrinsically Disordered Proteins: On the Accuracy of the TIP4P‐D Water Model and the Representativeness of Protein Disorder Models

Henriques, Joao LU and Skepö, Marie LU orcid (2016) In Journal of Chemical Theory and Computation 12(7). p.3407-3415
Abstract
Here, we first present a follow-up to a previous work by our group on the problematic of molecular dynamics simulations of intrinsically disordered proteins (IDPs) [Henriques et al. J. Chem. Theory Comput. 2015, 11, 3420−3431], using the recently developed TIP4P-D water model. When used in conjunction with the standard AMBER ff99SB-ILDN force field and applied to the simulation of Histatin 5, our IDP model, we obtain results which are in excellent agreement with the best performing IDP-suitable force field from the earlier study and with experiment. We then assess the representativeness of the IDP models used in these and similar studies, finding that most are too short in comparison to the average IDP and contain a bias toward hydrophilic... (More)
Here, we first present a follow-up to a previous work by our group on the problematic of molecular dynamics simulations of intrinsically disordered proteins (IDPs) [Henriques et al. J. Chem. Theory Comput. 2015, 11, 3420−3431], using the recently developed TIP4P-D water model. When used in conjunction with the standard AMBER ff99SB-ILDN force field and applied to the simulation of Histatin 5, our IDP model, we obtain results which are in excellent agreement with the best performing IDP-suitable force field from the earlier study and with experiment. We then assess the representativeness of the IDP models used in these and similar studies, finding that most are too short in comparison to the average IDP and contain a bias toward hydrophilic amino acid residues. Moreover, several key order- and disorder-promoting residues are also found to be misrepresented. It seems appropriate for future studies to address these issues. (Less)
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author
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organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Chemical Theory and Computation
volume
12
issue
7
pages
9 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • scopus:84978808769
  • pmid:27243806
  • wos:000379703800039
ISSN
1549-9618
DOI
10.1021/acs.jctc.6b00429
language
English
LU publication?
yes
id
7066c7b2-1a3b-4904-b8c1-60ebc3be1cff
date added to LUP
2016-10-21 13:57:45
date last changed
2025-04-04 15:22:33
@article{7066c7b2-1a3b-4904-b8c1-60ebc3be1cff,
  abstract     = {{Here, we first present a follow-up to a previous work by our group on the problematic of molecular dynamics simulations of intrinsically disordered proteins (IDPs) [Henriques et al. J. Chem. Theory Comput. 2015, 11, 3420−3431], using the recently developed TIP4P-D water model. When used in conjunction with the standard AMBER ff99SB-ILDN force field and applied to the simulation of Histatin 5, our IDP model, we obtain results which are in excellent agreement with the best performing IDP-suitable force field from the earlier study and with experiment. We then assess the representativeness of the IDP models used in these and similar studies, finding that most are too short in comparison to the average IDP and contain a bias toward hydrophilic amino acid residues. Moreover, several key order- and disorder-promoting residues are also found to be misrepresented. It seems appropriate for future studies to address these issues.}},
  author       = {{Henriques, Joao and Skepö, Marie}},
  issn         = {{1549-9618}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{7}},
  pages        = {{3407--3415}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Journal of Chemical Theory and Computation}},
  title        = {{Molecular Dynamics Simulations of Intrinsically Disordered Proteins: On the Accuracy of the TIP4P‐D Water Model and the Representativeness of Protein Disorder Models}},
  url          = {{http://dx.doi.org/10.1021/acs.jctc.6b00429}},
  doi          = {{10.1021/acs.jctc.6b00429}},
  volume       = {{12}},
  year         = {{2016}},
}