Comparison of MM/GBSA calculations based on explicit and implicit solvent simulations.
Godschalk, Frithjof ; Genheden, Samuel LU ; Söderhjelm, Pär LU and Ryde, Ulf LU
(2013)
In Physical Chemistry Chemical Physics
15(20).
p.7731-7739
- Abstract
- Molecular mechanics with generalised Born and surface area solvation (MM/GBSA) is a popular method to calculate the free energy of the binding of ligands to proteins. It involves molecular dynamics (MD) simulations with an explicit solvent of the protein-ligand complex to give a set of snapshots for which energies are calculated with an implicit solvent. This change in the solvation method (explicit → implicit) would strictly require that the energies are reweighted with the implicit-solvent energies, which is normally not done. In this paper we calculate MM/GBSA energies with two generalised Born models for snapshots generated by the same methods or by explicit-solvent simulations for five synthetic N-acetyllactosamine derivatives binding... (More)
- Molecular mechanics with generalised Born and surface area solvation (MM/GBSA) is a popular method to calculate the free energy of the binding of ligands to proteins. It involves molecular dynamics (MD) simulations with an explicit solvent of the protein-ligand complex to give a set of snapshots for which energies are calculated with an implicit solvent. This change in the solvation method (explicit → implicit) would strictly require that the energies are reweighted with the implicit-solvent energies, which is normally not done. In this paper we calculate MM/GBSA energies with two generalised Born models for snapshots generated by the same methods or by explicit-solvent simulations for five synthetic N-acetyllactosamine derivatives binding to galectin-3. We show that the resulting energies are very different both in absolute and relative terms, showing that the change in the solvent model is far from innocent and that standard MM/GBSA is not a consistent method. The ensembles generated with the various solvent models are quite different with root-mean-square deviations of 1.2-1.4 Å. The ensembles can be converted to each other by performing short MD simulations with the new method, but the convergence is slow, showing mean absolute differences in the calculated energies of 6-7 kJ mol(-1) after 2 ps simulations. Minimisations show even slower convergence and there are strong indications that the energies obtained from minimised structures are different from those obtained by MD. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3733665
- author
- Godschalk, Frithjof
; Genheden, Samuel
LU
; Söderhjelm, Pär
LU
and Ryde, Ulf
LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Physical Chemistry Chemical Physics
- volume
- 15
- issue
- 20
- pages
- 7731 - 7739
- publisher
- Royal Society of Chemistry
- external identifiers
-
- wos:000318306100039
- pmid:23595060
- scopus:84877283815
- pmid:23595060
- ISSN
- 1463-9084
- DOI
- 10.1039/c3cp00116d
- 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
- 4c080019-196f-4460-9e79-d1122e86b6b3 (old id 3733665)
- date added to LUP
- 2016-04-01 09:52:36
- date last changed
- 2023-01-01 22:58:55
@article{4c080019-196f-4460-9e79-d1122e86b6b3,
abstract = {{Molecular mechanics with generalised Born and surface area solvation (MM/GBSA) is a popular method to calculate the free energy of the binding of ligands to proteins. It involves molecular dynamics (MD) simulations with an explicit solvent of the protein-ligand complex to give a set of snapshots for which energies are calculated with an implicit solvent. This change in the solvation method (explicit → implicit) would strictly require that the energies are reweighted with the implicit-solvent energies, which is normally not done. In this paper we calculate MM/GBSA energies with two generalised Born models for snapshots generated by the same methods or by explicit-solvent simulations for five synthetic N-acetyllactosamine derivatives binding to galectin-3. We show that the resulting energies are very different both in absolute and relative terms, showing that the change in the solvent model is far from innocent and that standard MM/GBSA is not a consistent method. The ensembles generated with the various solvent models are quite different with root-mean-square deviations of 1.2-1.4 Å. The ensembles can be converted to each other by performing short MD simulations with the new method, but the convergence is slow, showing mean absolute differences in the calculated energies of 6-7 kJ mol(-1) after 2 ps simulations. Minimisations show even slower convergence and there are strong indications that the energies obtained from minimised structures are different from those obtained by MD.}},
author = {{Godschalk, Frithjof and Genheden, Samuel and Söderhjelm, Pär and Ryde, Ulf}},
issn = {{1463-9084}},
language = {{eng}},
number = {{20}},
pages = {{7731--7739}},
publisher = {{Royal Society of Chemistry}},
series = {{Physical Chemistry Chemical Physics}},
title = {{Comparison of MM/GBSA calculations based on explicit and implicit solvent simulations.}},
url = {{https://lup.lub.lu.se/search/files/1346513/4226425.pdf}},
doi = {{10.1039/c3cp00116d}},
volume = {{15}},
year = {{2013}},
}