MODELING MEMBRANE-PROTEINS USING STRUCTURAL RESTRAINTS

Here we present a procedure for. modelling membrane proteins which emp loys molecular dynamics simulations incorporating target restraints de rived from low-resolution structures alongside distance restraints der ived from mutagenesis data. Tire application of the modelling procedur e to the closed conformation of the pore domain of the nicotinic acety lcholine receptor is described. This domain is formed by a parallel bu ndle of five M2 helices. Each M2 helix is kinked due to cumulative dis tortions of backbone (phi,psi) values. The central region of M2 may ad opt a more distorted conformation. This would enable a ring of conserv ed leucine residues (one from each M2 helix) to pack together, occludi ng the central pole and thus preventing ion permeation. Molecular dyna mics simulations oil isolated helices that kink formation is not an in herent property of M2.