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Ligand affinities predicted with the MM/PBSA method: Dependence on the simulation method and the force field

Weis, Aaron ; Katebzadeh, Kambiz LU ; Söderhjelm, Pär LU ; Nilsson, Ingemar and Ryde, Ulf LU orcid (2006) In Journal of Medicinal Chemistry 49(22). p.6596-6606
Abstract
The free energy of binding between avidin and seven biotin analogues has been calculated with the molecular mechanics Poisson- Boltzmann surface area (MM/PBSA) method. We have studied how the force field and the method to generate geometries affect the calculated binding free energies. Four different force fields were compared, but we saw no significant difference in the results. However, mixing the force fields used for the geometry generation and energy calculations is not recommended. In the molecular dynamics simulations, explicit water molecules must be used, but the size of the simulated system and the boundary conditions are less important. In fact, nonperiodic simulations with a fixed protein outside a relatively small simulated... (More)
The free energy of binding between avidin and seven biotin analogues has been calculated with the molecular mechanics Poisson- Boltzmann surface area (MM/PBSA) method. We have studied how the force field and the method to generate geometries affect the calculated binding free energies. Four different force fields were compared, but we saw no significant difference in the results. However, mixing the force fields used for the geometry generation and energy calculations is not recommended. In the molecular dynamics simulations, explicit water molecules must be used, but the size of the simulated system and the boundary conditions are less important. In fact, nonperiodic simulations with a fixed protein outside a relatively small simulated system (18 angstrom) seem to be a proper approach. The mean absolute error was 9-19 kJ/mol, with a standard error of 5-15 kJ/mol, which arises mainly from the entropy term. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Medicinal Chemistry
volume
49
issue
22
pages
6596 - 6606
publisher
The American Chemical Society (ACS)
external identifiers
  • wos:000241553700018
  • scopus:33750467966
  • pmid:17064078
ISSN
1520-4804
DOI
10.1021/jm0608210
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
30162418-2c51-4d04-bace-95702ba53b88 (old id 378796)
date added to LUP
2016-04-01 12:27:17
date last changed
2021-10-03 04:26:33
@article{30162418-2c51-4d04-bace-95702ba53b88,
  abstract     = {The free energy of binding between avidin and seven biotin analogues has been calculated with the molecular mechanics Poisson- Boltzmann surface area (MM/PBSA) method. We have studied how the force field and the method to generate geometries affect the calculated binding free energies. Four different force fields were compared, but we saw no significant difference in the results. However, mixing the force fields used for the geometry generation and energy calculations is not recommended. In the molecular dynamics simulations, explicit water molecules must be used, but the size of the simulated system and the boundary conditions are less important. In fact, nonperiodic simulations with a fixed protein outside a relatively small simulated system (18 angstrom) seem to be a proper approach. The mean absolute error was 9-19 kJ/mol, with a standard error of 5-15 kJ/mol, which arises mainly from the entropy term.},
  author       = {Weis, Aaron and Katebzadeh, Kambiz and Söderhjelm, Pär and Nilsson, Ingemar and Ryde, Ulf},
  issn         = {1520-4804},
  language     = {eng},
  number       = {22},
  pages        = {6596--6606},
  publisher    = {The American Chemical Society (ACS)},
  series       = {Journal of Medicinal Chemistry},
  title        = {Ligand affinities predicted with the MM/PBSA method: Dependence on the simulation method and the force field},
  url          = {http://dx.doi.org/10.1021/jm0608210},
  doi          = {10.1021/jm0608210},
  volume       = {49},
  year         = {2006},
}