Can MM/GBSA calculations be sped up by system truncation?
Misini Ignjatović, Majda LU ; Mikulskis, Paulius LU ; Söderhjelm, Pär LU and Ryde, Ulf LU
(2018)
In Journal of Computational Chemistry
39(7).
p.361-372
- Abstract
We have studied whether calculations of the binding free energy of small ligands to a protein by the MM/GBSA approach (molecular mechanics combined with generalized Born and surface area solvation) can be sped up by including only a restricted number of atoms close to the ligand. If the protein is truncated before the molecular dynamics (MD) simulations, quite large changes are observed for the calculated binding energies, for example, 4 kJ/mol average difference for a radius of 19 Å for the binding of nine phenol derivatives to ferritin. The results are improved if no atoms are fixed in the simulations, with average and maximum errors of 2 and 3 kJ/mol at 19 Å and 3 and 6 kJ/mol at 7 Å. Similar results are obtained for two additional... (More)
We have studied whether calculations of the binding free energy of small ligands to a protein by the MM/GBSA approach (molecular mechanics combined with generalized Born and surface area solvation) can be sped up by including only a restricted number of atoms close to the ligand. If the protein is truncated before the molecular dynamics (MD) simulations, quite large changes are observed for the calculated binding energies, for example, 4 kJ/mol average difference for a radius of 19 Å for the binding of nine phenol derivatives to ferritin. The results are improved if no atoms are fixed in the simulations, with average and maximum errors of 2 and 3 kJ/mol at 19 Å and 3 and 6 kJ/mol at 7 Å. Similar results are obtained for two additional proteins, p38α MAP kinase and factor Xa. On the other hand, if energies are calculated on snapshots that are truncated after the MD simulation, all residues more than 8.5 Å from the ligand can be omitted without changing the energies by more than 1 kJ/mol on average (maximum error 1.4 kJ/mol). At the molecular mechanics level, the gain in computer time for such an approach is small. However, it shows what size of system should be used if the energies instead are calculated with a more demanding method, for example, quantum-mechanics.
(Less)
- author
- Misini Ignjatović, Majda
LU
; Mikulskis, Paulius
LU
; Söderhjelm, Pär
LU
and Ryde, Ulf
LU
- organization
- publishing date
- 2018-03-15
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- factor Xa, ferritin, ligand-binding affinities, MM/GBSA, p38α MAP kinase, system truncation
- in
- Journal of Computational Chemistry
- volume
- 39
- issue
- 7
- pages
- 12 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:29178493
- scopus:85035062929
- ISSN
- 0192-8651
- DOI
- 10.1002/jcc.25120
- language
- English
- LU publication?
- yes
- id
- dfd63698-d939-4af2-980a-e4831791b444
- date added to LUP
- 2018-02-08 07:41:46
- date last changed
- 2024-05-13 05:02:39
@article{dfd63698-d939-4af2-980a-e4831791b444,
abstract = {{<p>We have studied whether calculations of the binding free energy of small ligands to a protein by the MM/GBSA approach (molecular mechanics combined with generalized Born and surface area solvation) can be sped up by including only a restricted number of atoms close to the ligand. If the protein is truncated before the molecular dynamics (MD) simulations, quite large changes are observed for the calculated binding energies, for example, 4 kJ/mol average difference for a radius of 19 Å for the binding of nine phenol derivatives to ferritin. The results are improved if no atoms are fixed in the simulations, with average and maximum errors of 2 and 3 kJ/mol at 19 Å and 3 and 6 kJ/mol at 7 Å. Similar results are obtained for two additional proteins, p38α MAP kinase and factor Xa. On the other hand, if energies are calculated on snapshots that are truncated after the MD simulation, all residues more than 8.5 Å from the ligand can be omitted without changing the energies by more than 1 kJ/mol on average (maximum error 1.4 kJ/mol). At the molecular mechanics level, the gain in computer time for such an approach is small. However, it shows what size of system should be used if the energies instead are calculated with a more demanding method, for example, quantum-mechanics.</p>}},
author = {{Misini Ignjatović, Majda and Mikulskis, Paulius and Söderhjelm, Pär and Ryde, Ulf}},
issn = {{0192-8651}},
keywords = {{factor Xa; ferritin; ligand-binding affinities; MM/GBSA; p38α MAP kinase; system truncation}},
language = {{eng}},
month = {{03}},
number = {{7}},
pages = {{361--372}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Journal of Computational Chemistry}},
title = {{Can MM/GBSA calculations be sped up by system truncation?}},
url = {{https://lup.lub.lu.se/search/files/42439687/230_mmgbsa_trunc.pdf}},
doi = {{10.1002/jcc.25120}},
volume = {{39}},
year = {{2018}},
}