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Laboratory of Molecular Biophysics
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Previous: Channel Gating Mechanisms, Next: Bacterial Outer Membrane Proteins, Up: Ion Channels, Return to: Contents.
A number of simple (ca. 100 residue) membrane proteins encoded by viruses are believed to form ion channels. These include M2 (influenza A), NB (influenza B), CM2 (influenza C) and Vpu (Hiv-1). Combined modelling and simulation studies are being used to explore these further.
Molecular dynamics simulations on different length peptides of the membrane-spanning domain of the M2 protein from influenza A virus, were carried out within a lipid bilayer environment, leading to prediction of a 22-residue transmembrane domain [10]. Models were then generated for helical bundles of this length, whilst exploring the effect of different initial conditions [11]. Lipid bilayer simulations, combined with results from continuum electrostatics calculations, have provided some supporting evidence for a role of His37 residue in low-pH activation via a ring-flip mechanism. The dynamic motion of water molecules is reduced within the pore region, as expected for proton transport via the Grotthus mechanism.
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Nanosecond MD 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
unfavourable 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 [12]. The channel-forming
properties of the transmembrane peptide from NB have been studied by
measurement of ionic currents across planar bilayers, in parallel with
spectroscopic investigations to define the conformation of the NB TM segment as
a function of environment. Molecular models have been generated of NB helix
bundles, and the predicted properties of these have been compared with those of
the NB peptide induced channels [13].
Previous: Channel Gating Mechanisms, Next: Bacterial Outer Membrane Proteins, Up: Ion Channels, Return to: Contents.