How to obtain statistically converged MM/GBSA results.
Genheden, Samuel LU and Ryde, Ulf LU
(2010)
In Journal of Computational Chemistry
31(Online 13 Jul 2009).
p.837-846
- Abstract
- The molecular mechanics/generalized Born surface area (MM/GBSA) method has been investigated with the aim of achieving a statistical precision of 1 kJ/mol for the results. We studied the binding of seven biotin analogues to avidin, taking advantage of the fact that the protein is a tetramer with four independent binding sites, which should give the same estimated binding affinities. We show that it is not enough to use a single long simulation (10 ns), because the standard error of such a calculation underestimates the difference between the four binding sites. Instead, it is better to run several independent simulations and average the results. With such an approach, we obtain the same results for the four binding sites, and any desired... (More)
- The molecular mechanics/generalized Born surface area (MM/GBSA) method has been investigated with the aim of achieving a statistical precision of 1 kJ/mol for the results. We studied the binding of seven biotin analogues to avidin, taking advantage of the fact that the protein is a tetramer with four independent binding sites, which should give the same estimated binding affinities. We show that it is not enough to use a single long simulation (10 ns), because the standard error of such a calculation underestimates the difference between the four binding sites. Instead, it is better to run several independent simulations and average the results. With such an approach, we obtain the same results for the four binding sites, and any desired precision can be obtained by running a proper number of simulations. We discuss how the simulations should be performed to optimize the use of computer time. The correlation time between the MM/GBSA energies is approximately 5 ps and an equilibration time of 100 ps is needed. For MM/GBSA, we recommend a sampling time of 20-200 ps for each separate simulation, depending on the protein. With 200 ps production time, 5-50 separate simulations are required to reach a statistical precision of 1 kJ/mol (800-8000 energy calculations or 1.5-15 ns total simulation time per ligand) for the seven avidin ligands. This is an order of magnitude more than what is normally used, but such a number of simulations is needed to obtain statistically valid results for the MM/GBSA method. (c) 2009 Wiley Periodicals, Inc. J Comput Chem 2009. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1453106
- author
- Genheden, Samuel
LU
and Ryde, Ulf
LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Computational Chemistry
- volume
- 31
- issue
- Online 13 Jul 2009
- pages
- 837 - 846
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000274922000015
- pmid:19598265
- scopus:76249085850
- pmid:19598265
- ISSN
- 1096-987X
- DOI
- 10.1002/jcc.21366
- 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
- 71487c85-2ad9-469a-9bcf-90da72883fb7 (old id 1453106)
- date added to LUP
- 2016-04-01 13:35:08
- date last changed
- 2023-02-07 02:35:14
@article{71487c85-2ad9-469a-9bcf-90da72883fb7,
abstract = {{The molecular mechanics/generalized Born surface area (MM/GBSA) method has been investigated with the aim of achieving a statistical precision of 1 kJ/mol for the results. We studied the binding of seven biotin analogues to avidin, taking advantage of the fact that the protein is a tetramer with four independent binding sites, which should give the same estimated binding affinities. We show that it is not enough to use a single long simulation (10 ns), because the standard error of such a calculation underestimates the difference between the four binding sites. Instead, it is better to run several independent simulations and average the results. With such an approach, we obtain the same results for the four binding sites, and any desired precision can be obtained by running a proper number of simulations. We discuss how the simulations should be performed to optimize the use of computer time. The correlation time between the MM/GBSA energies is approximately 5 ps and an equilibration time of 100 ps is needed. For MM/GBSA, we recommend a sampling time of 20-200 ps for each separate simulation, depending on the protein. With 200 ps production time, 5-50 separate simulations are required to reach a statistical precision of 1 kJ/mol (800-8000 energy calculations or 1.5-15 ns total simulation time per ligand) for the seven avidin ligands. This is an order of magnitude more than what is normally used, but such a number of simulations is needed to obtain statistically valid results for the MM/GBSA method. (c) 2009 Wiley Periodicals, Inc. J Comput Chem 2009.}},
author = {{Genheden, Samuel and Ryde, Ulf}},
issn = {{1096-987X}},
language = {{eng}},
number = {{Online 13 Jul 2009}},
pages = {{837--846}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Journal of Computational Chemistry}},
title = {{How to obtain statistically converged MM/GBSA results.}},
url = {{https://lup.lub.lu.se/search/files/136743693/134_mmgbsa.pdf}},
doi = {{10.1002/jcc.21366}},
volume = {{31}},
year = {{2010}},
}