Viral ion channels: molecular modeling and simulation

Sansom, Mark S. P.; Forrest, Lucy R.; Bull, Richard M. R.

doi:10.1002/(sici)1521-1878(199812)20:12<992::aid-bies5>3.0.co;2-7

Cited by 26 publications

(14 citation statements)

References 66 publications

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“…This choice leaves the S residue facing toward the lipid bilayer. This setup is in agreement with experimental measurements by Arkin and co-workers, but differs from the choice made by Sansom et al, (Kukol and Arkin, 1999;Sansom et al, 1998). Once the peptide bundle was inserted into the bilayer, as shown in Fig.…”

Section: Initial Conditionssupporting

confidence: 90%

“…The orientation of these domains has been confirmed for VPU and other ion channels by using NMR to probe the tilt angle (Zheng et al, 2001;Marassi and Opella, 2000). Computational approaches to the elucidation of the structure of TM proteins have also shown that small proteins topologically similar to VPU will align more or less perpendicular to the bilayer surface (Sansom et al, 1998).…”

Section: Introductionmentioning

confidence: 91%

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Molecular Dynamics Investigation of Membrane-Bound Bundles of the Channel-Forming Transmembrane Domain of Viral Protein U from the Human Immunodeficiency Virus HIV-1

López

Montal

Blasie

et al. 2002

Biophysical Journal

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Molecular dynamics (MD) simulations have been carried out on bundles of the channel-forming transmembrane (TM) domain of the viral protein U (VPU(1-27) and VPU(6-27)) from the human immunodeficiency virus (HIV-1). Simulations of hexameric and pentameric bundles of VPU(6-27) in an octane/water membrane mimetic system suggested that the pentamer is the preferred oligomer. Accordingly, an unconstrained pentameric helix bundle of VPU(1-27) was then placed in a hydrated palmitoyl-oleyl-3-n-glycero-phosphatidylethanolamine (POPE) lipid bilayer and its structural properties calculated from a 3-ns MD run. Some water molecules, initially inside the channel lumen, were expelled halfway through the simulation and the bundle adopted a conical structure reminiscent of previous MD results obtained for VPU(6-27) in an octane/water system. The pore constriction generated may correspond to a closed state of the channel and underlies the relocation of the W residue toward the pore lumen. The relative positions of the helices with respect to the bilayer and their interactions with the lipids are discussed. The observed structure is stabilized via specific interactions between the VPU helices and the carbonyl oxygen atoms of the lipid molecules, particularly at the Q and S residues.

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Section: Initial Conditionssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 91%

Molecular Dynamics Investigation of Membrane-Bound Bundles of the Channel-Forming Transmembrane Domain of Viral Protein U from the Human Immunodeficiency Virus HIV-1

López

Montal

Blasie

et al. 2002

Biophysical Journal

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“…The M2 channel protein from influenza A virus ( Fig. 1) provides a good test case for modeling studies of simple membrane proteins (34,35). It is a 97-residue protein containing a single TM a-helix.…”

Section: Introductionmentioning

confidence: 99%

Self-Assembly of a Simple Membrane Protein: Coarse-Grained Molecular Dynamics Simulations of the Influenza M2 Channel

Carpenter

Bond²,

Khalid³

et al. 2008

Biophysical Journal

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The transmembrane (TM) domain of the M2 channel protein from influenza A is a homotetrameric bundle of alpha-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 x 5 micros) 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 2x rotationally symmetrical packing of the helices. The helices form a left-handed bundle, with a helix tilt angle of approximately 16 degrees. 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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“…A relatively simple class of ion channels is provided by a number of virally encoded membrane proteins 7, 8. These may provide a paradigm for ion channel folding and assembly.…”

Section: Introductionmentioning

confidence: 99%

Transmembrane domains of viral ion channel proteins: A molecular dynamics simulation study

Fischer¹,

Forrest²,

Smith³

et al. 2000

Biopolymers

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Nanosecond molecular dynamics simulations in a fully solvated phospholipid bilayer have been performed on single transmembrane ␣-helices from three putative ion channel proteins encoded by viruses: NB (from influenza B), CM2 (from influenza C), and Vpu (from HIV-1). ␣-Helix stability is maintained within a core region of ca. 28 residues for each protein. Helix perturbations are due either to unfavorable interactions of hydrophobic residues with the lipid headgroups or to the need of the termini of short helices to extend into the surrounding interfacial environment in order to form H-bonds. The requirement of both ends of a helix to form favorable interactions with lipid headgroups and/or water may also lead to tilting and/or kinking of a transmembrane ␣-helix.Residues that are generally viewed as poor helix formers in aqueous solution (e.g., Gly, Ile, Val) do not destabilize helices, if located within a helix that spans a lipid bilayer. However, helix/bilayer mismatch such that a helix ends abruptly within the bilayer core destabilizes the end of the helix, especially in the presence of Gly and Ala residues. Hydrogen bonding of polar side-chains with the peptide backbone and with one another occurs when such residues are present within the bilayer core, thus minimizing the energetic cost of burying such side-chains.

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Viral ion channels: molecular modeling and simulation

Cited by 26 publications

References 66 publications

Molecular Dynamics Investigation of Membrane-Bound Bundles of the Channel-Forming Transmembrane Domain of Viral Protein U from the Human Immunodeficiency Virus HIV-1

Molecular Dynamics Investigation of Membrane-Bound Bundles of the Channel-Forming Transmembrane Domain of Viral Protein U from the Human Immunodeficiency Virus HIV-1

Self-Assembly of a Simple Membrane Protein: Coarse-Grained Molecular Dynamics Simulations of the Influenza M2 Channel

Transmembrane domains of viral ion channel proteins: A molecular dynamics simulation study

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