Modelling membrane proteins using structural restraints.
Here we present a procedure for modelling membrane proteins which employs molecular dynamics simulations incorporating target restraints derived from low-resolution structures alongside distance restraints derived from mutagenesis data. The application of the modelling procedure to the closed conformation of the pore domain of the nicotinic acetylcholine receptor is described. This domain is formed by a parallel bundle of five M2 helices. Each M2 helix is kinked due to cumulative distortions of backbone (phi, psi) values. The central region of M2 may adopt a more distorted conformation. This would enable a ring of conserved leucine residues (one from each M2 helix) to pack together, occluding the central pore and thus preventing ion permeation. Molecular dynamics simulations on isolated helices that kink formation is not an inherent property of M2.
Sansom
M S
MS
Laboratory of Molecular Biophysics, University of Oxford, UK.
Sankararamakrishnan
R
R
Kerr
I D
ID
D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009474:Neurons / Q000378:metabolism; D017433:Protein Structure, Secondary; D011978:Receptors, Nicotinic / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D013314:Stress, Mechanical
D008565:Membrane Proteins; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins