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Starting-Condition Dependence of Order Parameters Derived from Molecular Dynamics Simulations

Genheden, Samuel LU ; Diehl, Carl LU ; Akke, Mikael LU and Ryde, Ulf LU (2010) In Journal of Chemical Theory and Computation 6(7). p.2176-2190
Abstract
We have studied how backbone N-H S-2 order parameters calculated from molecular dynamics simulations depend on the method used to calculate them, the starting conditions, and the length of the simulations. Using the carbohydrate binding domain of galectin-3 in the free and lactose-bound states as a test case, we compared the calculated order parameters with experimental data from NMR relaxation. The results indicate that the sampling can be improved by using several starting structures, taking into account conformational heterogeneity reported in crystal structures. However, the improvement is rather limited, and for 93% of the dihedrals that have alternative conformations in the crystal structures, the conformational space is well sampled... (More)
We have studied how backbone N-H S-2 order parameters calculated from molecular dynamics simulations depend on the method used to calculate them, the starting conditions, and the length of the simulations. Using the carbohydrate binding domain of galectin-3 in the free and lactose-bound states as a test case, we compared the calculated order parameters with experimental data from NMR relaxation. The results indicate that the sampling can be improved by using several starting structures, taking into account conformational heterogeneity reported in crystal structures. However, the improvement is rather limited, and for 93% of the dihedrals that have alternative conformations in the crystal structures, the conformational space is well sampled even if a single conformation is used as the starting structure. Moreover, the agreement with experimental data is improved when using several short simulations, rather than a single long simulation. In the present case, we find that similar to 10 independent simulations provide sufficient sampling, and the ideal length of the simulations is similar to 10 ns, which is similar to 25% longer than the global correlation time for rotational diffusion. On the other hand, the equilibration time appears to be less important, and our results suggest that an equilibration time of 0.25 ns is sufficient. We have also compared four different methods to extract the order parameters from the simulations, namely, the autocorrelation function and isotropic reorientational eigenmode dynamics using three different window sizes. Overall, the four methods yield comparable results, but large differences between the methods may serve to pinpoint cases for which the calculated parameters are unreliable. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Chemical Theory and Computation
volume
6
issue
7
pages
2176 - 2190
publisher
The American Chemical Society
external identifiers
  • wos:000279751500025
  • scopus:79251636508
ISSN
1549-9618
DOI
10.1021/ct900696z
language
English
LU publication?
yes
id
d7afafa7-5119-4b9b-bb13-e6fefc7acefc (old id 1657920)
date added to LUP
2010-08-24 13:14:50
date last changed
2018-06-03 03:21:33
@article{d7afafa7-5119-4b9b-bb13-e6fefc7acefc,
  abstract     = {We have studied how backbone N-H S-2 order parameters calculated from molecular dynamics simulations depend on the method used to calculate them, the starting conditions, and the length of the simulations. Using the carbohydrate binding domain of galectin-3 in the free and lactose-bound states as a test case, we compared the calculated order parameters with experimental data from NMR relaxation. The results indicate that the sampling can be improved by using several starting structures, taking into account conformational heterogeneity reported in crystal structures. However, the improvement is rather limited, and for 93% of the dihedrals that have alternative conformations in the crystal structures, the conformational space is well sampled even if a single conformation is used as the starting structure. Moreover, the agreement with experimental data is improved when using several short simulations, rather than a single long simulation. In the present case, we find that similar to 10 independent simulations provide sufficient sampling, and the ideal length of the simulations is similar to 10 ns, which is similar to 25% longer than the global correlation time for rotational diffusion. On the other hand, the equilibration time appears to be less important, and our results suggest that an equilibration time of 0.25 ns is sufficient. We have also compared four different methods to extract the order parameters from the simulations, namely, the autocorrelation function and isotropic reorientational eigenmode dynamics using three different window sizes. Overall, the four methods yield comparable results, but large differences between the methods may serve to pinpoint cases for which the calculated parameters are unreliable.},
  author       = {Genheden, Samuel and Diehl, Carl and Akke, Mikael and Ryde, Ulf},
  issn         = {1549-9618},
  language     = {eng},
  number       = {7},
  pages        = {2176--2190},
  publisher    = {The American Chemical Society},
  series       = {Journal of Chemical Theory and Computation},
  title        = {Starting-Condition Dependence of Order Parameters Derived from Molecular Dynamics Simulations},
  url          = {http://dx.doi.org/10.1021/ct900696z},
  volume       = {6},
  year         = {2010},
}