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Self-assembly of a simple membrane protein: coarse-grained molecular dynamics simulations of the influenza M2 channel

Self-assembly of a simple membrane protein: coarse-grained molecular dynamics simulations of the influenza M2 channel
Self-assembly of a simple membrane protein: coarse-grained molecular dynamics simulations of the influenza M2 channel
The transmembrane (TM) domain of the M2 channel protein from influenza A is a homotetrameric bundle of ?-helices and provides a model system for computational approaches to self-assembly of membrane proteins. Coarse-grained molecular dynamics (CG-MD) simulations have been used to explore partitioning into a membrane of M2 TM helices during bilayer self-assembly from lipids. CG-MD is also used to explore tetramerization of preinserted M2 TM helices. The M2 helix monomer adopts a membrane spanning orientation in a lipid (DPPC) bilayer. Multiple extended CG-MD simulations (5 × 5 ?s) were used to study the tetramerization of inserted M2 helices. The resultant tetramers were evaluated in terms of the most populated conformations and the dynamics of their interconversion. This analysis reveals that the M2 tetramer has 2× rotationally symmetrical packing of the helices. The helices form a left-handed bundle, with a helix tilt angle of 16°. The M2 helix bundle generated by CG-MD was converted to an atomistic model. Simulations of this model reveal that the bundle's stability depends on the assumed protonation state of the H37 side chains. These simulations alongside comparison with recent x-ray (3BKD) and NMR (2RLF) structures of the M2 bundle suggest that the model yielded by CG-MD may correspond to a closed state of the channel
0006-3495
3790-3801
Carpenter, Timothy
b495994c-934e-4788-8f54-e4d47ddfeb1a
Bond, Peter J
f6fa881e-cc1e-496c-8811-3433968a9bca
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Sansom, Mark S.P
388f3589-c0a1-4c95-a4c3-0cc47d576bf2
Voth, Gregory A
399a3992-d899-4eaa-a167-382be41e34eb
Carpenter, Timothy
b495994c-934e-4788-8f54-e4d47ddfeb1a
Bond, Peter J
f6fa881e-cc1e-496c-8811-3433968a9bca
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Sansom, Mark S.P
388f3589-c0a1-4c95-a4c3-0cc47d576bf2
Voth, Gregory A
399a3992-d899-4eaa-a167-382be41e34eb

Carpenter, Timothy, Bond, Peter J, Khalid, Syma and Sansom, Mark S.P , Voth, Gregory A (ed.) (2008) Self-assembly of a simple membrane protein: coarse-grained molecular dynamics simulations of the influenza M2 channel. Biophysical Journal, 95 (8), 3790-3801. (doi:10.1529/biophysj.108.131078).

Record type: Article

Abstract

The transmembrane (TM) domain of the M2 channel protein from influenza A is a homotetrameric bundle of ?-helices and provides a model system for computational approaches to self-assembly of membrane proteins. Coarse-grained molecular dynamics (CG-MD) simulations have been used to explore partitioning into a membrane of M2 TM helices during bilayer self-assembly from lipids. CG-MD is also used to explore tetramerization of preinserted M2 TM helices. The M2 helix monomer adopts a membrane spanning orientation in a lipid (DPPC) bilayer. Multiple extended CG-MD simulations (5 × 5 ?s) were used to study the tetramerization of inserted M2 helices. The resultant tetramers were evaluated in terms of the most populated conformations and the dynamics of their interconversion. This analysis reveals that the M2 tetramer has 2× rotationally symmetrical packing of the helices. The helices form a left-handed bundle, with a helix tilt angle of 16°. The M2 helix bundle generated by CG-MD was converted to an atomistic model. Simulations of this model reveal that the bundle's stability depends on the assumed protonation state of the H37 side chains. These simulations alongside comparison with recent x-ray (3BKD) and NMR (2RLF) structures of the M2 bundle suggest that the model yielded by CG-MD may correspond to a closed state of the channel

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Published date: 15 October 2008

Identifiers

Local EPrints ID: 149551
URI: https://eprints.soton.ac.uk/id/eprint/149551
ISSN: 0006-3495
PURE UUID: 4ed8aa4d-4f51-492d-b385-9e79bd69cc64
ORCID for Syma Khalid: ORCID iD orcid.org/0000-0002-3694-5044

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Date deposited: 30 Apr 2010 13:14
Last modified: 05 Nov 2019 01:45

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