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The Effect of Force-Field Parameters on Cytochrome P450-Membrane Interactions: Structure and Dynamics

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 in...

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Autores principales: Mustafa, Ghulam, Nandekar, Prajwal P., Mukherjee, Goutam, Bruce, Neil J., Wade, Rebecca C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190701/
https://www.ncbi.nlm.nih.gov/pubmed/32350331
http://dx.doi.org/10.1038/s41598-020-64129-7
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author Mustafa, Ghulam
Nandekar, Prajwal P.
Mukherjee, Goutam
Bruce, Neil J.
Wade, Rebecca C.
author_facet Mustafa, Ghulam
Nandekar, Prajwal P.
Mukherjee, Goutam
Bruce, Neil J.
Wade, Rebecca C.
author_sort Mustafa, Ghulam
collection PubMed
description 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.
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spelling pubmed-71907012020-05-05 The Effect of Force-Field Parameters on Cytochrome P450-Membrane Interactions: Structure and Dynamics Mustafa, Ghulam Nandekar, Prajwal P. Mukherjee, Goutam Bruce, Neil J. Wade, Rebecca C. Sci Rep Article 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. Nature Publishing Group UK 2020-04-29 /pmc/articles/PMC7190701/ /pubmed/32350331 http://dx.doi.org/10.1038/s41598-020-64129-7 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Mustafa, Ghulam
Nandekar, Prajwal P.
Mukherjee, Goutam
Bruce, Neil J.
Wade, Rebecca C.
The Effect of Force-Field Parameters on Cytochrome P450-Membrane Interactions: Structure and Dynamics
title The Effect of Force-Field Parameters on Cytochrome P450-Membrane Interactions: Structure and Dynamics
title_full The Effect of Force-Field Parameters on Cytochrome P450-Membrane Interactions: Structure and Dynamics
title_fullStr The Effect of Force-Field Parameters on Cytochrome P450-Membrane Interactions: Structure and Dynamics
title_full_unstemmed The Effect of Force-Field Parameters on Cytochrome P450-Membrane Interactions: Structure and Dynamics
title_short The Effect of Force-Field Parameters on Cytochrome P450-Membrane Interactions: Structure and Dynamics
title_sort effect of force-field parameters on cytochrome p450-membrane interactions: structure and dynamics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190701/
https://www.ncbi.nlm.nih.gov/pubmed/32350331
http://dx.doi.org/10.1038/s41598-020-64129-7
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