Ligand affinities predicted with the MM/PBSA method: Dependence on the simulation method and the force field
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/378796
- author
- Weis, Aaron ; Katebzadeh, Kambiz LU ; Söderhjelm, Pär LU ; Nilsson, Ingemar and Ryde, Ulf LU
- organization
- publishing date
- 2006
- 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
- 2023-01-24 02:30:30
@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 = {{https://lup.lub.lu.se/search/files/135493844/90_mmpbsa.pdf}}, doi = {{10.1021/jm0608210}}, volume = {{49}}, year = {{2006}}, }