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Title: On the application of the MARTINI coarse-grained model to immersion of a protein in a phospholipid bilayer

Abstract

An important step in the simulation of a membrane protein in a phospholipid bilayer is the correct immersion of the protein in the bilayer. Crystal structures are determined without the bilayer. Particularly for proteins with monotopic domains, it can be unclear how deeply and in which orientation the protein is being inserted in the membrane. We have previously developed a procedure combining coarse-grain (CG) with all-atom (AA) molecular dynamics (MD) simulations to insert and simulate a cytochrome P450 (CYP) possessing an N-terminal transmembrane helix connected by a flexible linker region to a globular domain that dips into the membrane. The CG simulations provide a computationally efficient means to explore different orientations and conformations of the CYP in the membrane. Converged configurations obtained in the CG simulations are then refined in AA simulations. Here, we tested different variants of the MARTINI CG model, differing in the water model, the treatment of long-range non-bonded interactions, and the implementation (GROMACS 4.5.5 vs 5.0.4), for this purpose. We examined the behavior of the models for simulating a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer in water and for the immersion of CYP3A4 in a POPC bilayer, and compared the CG-MD results with the previously reported experimental and simulationmore » results. We also tested the methodology on a set of four other CYPs. Finally, we propose an optimized protocol for modeling such protein-membrane systems that provides the most plausible configurations and is computationally efficient; this incorporates the standard non-polar water model and the GROMACS 5.0.4 implementation with a reaction field treatment of long-range interactions.« less

Authors:
; ;  [1]
  1. Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), Schloß-Wolfsbrunnenweg 35, 69118 Heidelberg (Germany)
Publication Date:
OSTI Identifier:
22493379
Resource Type:
Journal Article
Journal Name:
Journal of Chemical Physics
Additional Journal Information:
Journal Volume: 143; Journal Issue: 24; Other Information: (c) 2015 AIP Publishing LLC; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0021-9606
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; ATOMS; COMPARATIVE EVALUATIONS; CRYSTAL STRUCTURE; CYTOCHROMES; GRAIN SIZE; IMPLEMENTATION; INTERACTION RANGE; LAYERS; MEMBRANE PROTEINS; MEMBRANES; MOLECULAR DYNAMICS METHOD; ORIENTATION; PHOSPHOLIPIDS; WATER

Citation Formats

Mustafa, Ghulam, Nandekar, Prajwal P., Yu, Xiaofeng, Wade, Rebecca C., E-mail: Ghulam.Mustafa@h-its.org, E-mail: rebecca.wade@h-its.org, Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, INF 282, 69120 Heidelberg, and Interdisciplinary Center for Scientific Computing. On the application of the MARTINI coarse-grained model to immersion of a protein in a phospholipid bilayer. United States: N. p., 2015. Web. doi:10.1063/1.4936909.
Mustafa, Ghulam, Nandekar, Prajwal P., Yu, Xiaofeng, Wade, Rebecca C., E-mail: Ghulam.Mustafa@h-its.org, E-mail: rebecca.wade@h-its.org, Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, INF 282, 69120 Heidelberg, & Interdisciplinary Center for Scientific Computing. On the application of the MARTINI coarse-grained model to immersion of a protein in a phospholipid bilayer. United States. https://doi.org/10.1063/1.4936909
Mustafa, Ghulam, Nandekar, Prajwal P., Yu, Xiaofeng, Wade, Rebecca C., E-mail: Ghulam.Mustafa@h-its.org, E-mail: rebecca.wade@h-its.org, Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, INF 282, 69120 Heidelberg, and Interdisciplinary Center for Scientific Computing. 2015. "On the application of the MARTINI coarse-grained model to immersion of a protein in a phospholipid bilayer". United States. https://doi.org/10.1063/1.4936909.
@article{osti_22493379,
title = {On the application of the MARTINI coarse-grained model to immersion of a protein in a phospholipid bilayer},
author = {Mustafa, Ghulam and Nandekar, Prajwal P. and Yu, Xiaofeng and Wade, Rebecca C., E-mail: Ghulam.Mustafa@h-its.org, E-mail: rebecca.wade@h-its.org and Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, INF 282, 69120 Heidelberg and Interdisciplinary Center for Scientific Computing},
abstractNote = {An important step in the simulation of a membrane protein in a phospholipid bilayer is the correct immersion of the protein in the bilayer. Crystal structures are determined without the bilayer. Particularly for proteins with monotopic domains, it can be unclear how deeply and in which orientation the protein is being inserted in the membrane. We have previously developed a procedure combining coarse-grain (CG) with all-atom (AA) molecular dynamics (MD) simulations to insert and simulate a cytochrome P450 (CYP) possessing an N-terminal transmembrane helix connected by a flexible linker region to a globular domain that dips into the membrane. The CG simulations provide a computationally efficient means to explore different orientations and conformations of the CYP in the membrane. Converged configurations obtained in the CG simulations are then refined in AA simulations. Here, we tested different variants of the MARTINI CG model, differing in the water model, the treatment of long-range non-bonded interactions, and the implementation (GROMACS 4.5.5 vs 5.0.4), for this purpose. We examined the behavior of the models for simulating a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer in water and for the immersion of CYP3A4 in a POPC bilayer, and compared the CG-MD results with the previously reported experimental and simulation results. We also tested the methodology on a set of four other CYPs. Finally, we propose an optimized protocol for modeling such protein-membrane systems that provides the most plausible configurations and is computationally efficient; this incorporates the standard non-polar water model and the GROMACS 5.0.4 implementation with a reaction field treatment of long-range interactions.},
doi = {10.1063/1.4936909},
url = {https://www.osti.gov/biblio/22493379}, journal = {Journal of Chemical Physics},
issn = {0021-9606},
number = 24,
volume = 143,
place = {United States},
year = {Mon Dec 28 00:00:00 EST 2015},
month = {Mon Dec 28 00:00:00 EST 2015}
}