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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1756716
- author
- Genheden, Samuel
LU
and Ryde, Ulf
LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Computational Chemistry
- volume
- 32
- issue
- 2
- pages
- 187 - 195
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000285312300001
- pmid:21132839
- scopus:78149440040
- pmid:21132839
- ISSN
- 1096-987X
- DOI
- 10.1002/jcc.21546
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Theoretical Chemistry (S) (011001039)
- id
- 5663cbf3-f18c-4429-b4ec-1d0169d9cb1f (old id 1756716)
- date added to LUP
- 2016-04-01 15:02:42
- date last changed
- 2023-01-04 08:12:05
@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 Inc.}},
series = {{Journal of Computational Chemistry}},
title = {{A comparison of different initialization protocols to obtain statistically independent molecular dynamics simulations.}},
url = {{https://lup.lub.lu.se/search/files/4311019/2339570.pdf}},
doi = {{10.1002/jcc.21546}},
volume = {{32}},
year = {{2011}},
}