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A comparison of different initialization protocols to obtain statistically independent molecular dynamics simulations.

Genheden, Samuel LU and Ryde, Ulf LU (2011) In Journal of Computational Chemistry 32(2). p.187-195
Abstract
We study how the results of molecular dynamics (MD) simulations are affected by various choices during the setup, e.g., the starting velocities, the solvation, the location of protons, the conformation of His, Asn, and Gln residues, the protonation and titration of His residues, and the treatment of alternative conformations. We estimate the binding affinity of ligands to four proteins calculated with the MM/GBSA method (molecular mechanics combined with a generalized Born and surface area solvation energy). For avidin and T4 lysozyme, all variations gave similar results within 2 kJ/mol. For factor Xa, differences in the solvation or in the selection of alternative conformations gave results that are significantly different from those of... (More)
We study how the results of molecular dynamics (MD) simulations are affected by various choices during the setup, e.g., the starting velocities, the solvation, the location of protons, the conformation of His, Asn, and Gln residues, the protonation and titration of His residues, and the treatment of alternative conformations. We estimate the binding affinity of ligands to four proteins calculated with the MM/GBSA method (molecular mechanics combined with a generalized Born and surface area solvation energy). For avidin and T4 lysozyme, all variations gave similar results within 2 kJ/mol. For factor Xa, differences in the solvation or in the selection of alternative conformations gave results that are significantly different from those of the other approaches by 4-6 kJ/mol, whereas for galectin-3, changes in the conformations, rotations, and protonation gave results that differed by 10 kJ/mol, but only if residues close to the binding site were modified. This shows that the results of MM/GBSA calculations are reasonably reproducible even if the MD simulations are set up with different software. Moreover, we show that the sampling of phase space can be enhanced by solvating the systems with different equilibrated water boxes, in addition to the common use of different starting velocities. If different conformations are available in the crystal structure, they should also be employed to enhance the sampling. Protonation, ionization, and conformations of Asn, Gln, and His may also be used to enhance sampling, but great effort should be spent to obtain as reliable predictions as possible close to the active site. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Computational Chemistry
volume
32
issue
2
pages
187 - 195
publisher
John Wiley & Sons
external identifiers
  • wos:000285312300001
  • pmid:21132839
  • scopus:78149440040
ISSN
1096-987X
DOI
10.1002/jcc.21546
language
English
LU publication?
yes
id
5663cbf3-f18c-4429-b4ec-1d0169d9cb1f (old id 1756716)
date added to LUP
2010-12-30 11:13:39
date last changed
2017-05-21 04:13:20
@article{5663cbf3-f18c-4429-b4ec-1d0169d9cb1f,
  abstract     = {We study how the results of molecular dynamics (MD) simulations are affected by various choices during the setup, e.g., the starting velocities, the solvation, the location of protons, the conformation of His, Asn, and Gln residues, the protonation and titration of His residues, and the treatment of alternative conformations. We estimate the binding affinity of ligands to four proteins calculated with the MM/GBSA method (molecular mechanics combined with a generalized Born and surface area solvation energy). For avidin and T4 lysozyme, all variations gave similar results within 2 kJ/mol. For factor Xa, differences in the solvation or in the selection of alternative conformations gave results that are significantly different from those of the other approaches by 4-6 kJ/mol, whereas for galectin-3, changes in the conformations, rotations, and protonation gave results that differed by 10 kJ/mol, but only if residues close to the binding site were modified. This shows that the results of MM/GBSA calculations are reasonably reproducible even if the MD simulations are set up with different software. Moreover, we show that the sampling of phase space can be enhanced by solvating the systems with different equilibrated water boxes, in addition to the common use of different starting velocities. If different conformations are available in the crystal structure, they should also be employed to enhance the sampling. Protonation, ionization, and conformations of Asn, Gln, and His may also be used to enhance sampling, but great effort should be spent to obtain as reliable predictions as possible close to the active site.},
  author       = {Genheden, Samuel and Ryde, Ulf},
  issn         = {1096-987X},
  language     = {eng},
  number       = {2},
  pages        = {187--195},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Computational Chemistry},
  title        = {A comparison of different initialization protocols to obtain statistically independent molecular dynamics simulations.},
  url          = {http://dx.doi.org/10.1002/jcc.21546},
  volume       = {32},
  year         = {2011},
}