The Effect of Force-Field Parameters on Cytochrome P450-Membrane Interactions: Structure and Dynamics.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 04 2020
29 04 2020
Historique:
received:
05
08
2019
accepted:
13
04
2020
entrez:
1
5
2020
pubmed:
1
5
2020
medline:
25
11
2020
Statut:
epublish
Résumé
The simulation of membrane proteins requires compatible protein and lipid force fields that reproduce the properties of both the protein and the lipid bilayer. Cytochrome P450 enzymes are bitopic membrane proteins with a transmembrane helical anchor and a large cytosolic globular domain that dips into the membrane. As such, they are representative and challenging examples of membrane proteins for simulations, displaying features of both peripheral and integral membrane proteins. We performed molecular dynamics simulations of three cytochrome P450 isoforms (2C9, 2C19 and 1A1) in a 2-oleoyl-1-palmitoyl-sn-glycerol-3-phosphocholine bilayer using two AMBER force field combinations: GAFF-LIPID with ff99SB for the protein, and LIPID14 with ff14SB for the protein. Comparison of the structural and dynamic properties of the proteins, the lipids and the protein-membrane interactions shows differing sensitivity of the cytochrome P450 isoforms to the choice of force field, with generally better agreement with experiment for the LIPID14 + ff14SB combination.
Identifiants
pubmed: 32350331
doi: 10.1038/s41598-020-64129-7
pii: 10.1038/s41598-020-64129-7
pmc: PMC7190701
doi:
Substances chimiques
Lipid Bilayers
0
Membrane Lipids
0
Cytochrome P-450 Enzyme System
9035-51-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7284Références
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