The effect of force-field parameters on cytochrome P450-membrane interactions

• Verfasst von: Mustafa, Ghulam [VerfasserIn]
• Verfasst von: Nandekar, Prajwal [VerfasserIn]
• Verfasst von: Mukherjee, Goutam [VerfasserIn]
• Verfasst von: Bruce, Neil J. [VerfasserIn]
• Verfasst von: Wade, Rebecca C. [VerfasserIn]
• Titel: The effect of force-field parameters on cytochrome P450-membrane interactions
• Titelzusatz: structure and dynamics
• Verf.angabe: Ghulam Mustafa, Prajwal P. Nandekar, Goutam Mukherjee, Neil J. Bruc &, Rebecca C. Wade
• E-Jahr: 2020
• Jahr: 29 April 2020
• Fussnoten: Gesehen am 17.09.2020
• Titel Quelle: Enthalten in: Scientific reports
• Ort Quelle: [London] : Macmillan Publishers Limited, part of Springer Nature, 2011
• Jahr Quelle: 2020
• Band/Heft Quelle: 10(2020) Artikel-Nummer 7284, 11 Seiten
• ISSN Quelle: 2045-2322
• DOI: doi:10.1038/s41598-020-64129-7
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1733229450

Abstract

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.