title: The open state gating mechanism of gramicidin a requires relative opposed monomer rotation and simultaneous lateral displacement.
abstract: The gating mechanism of the open state of the gramicidin A (gA) channel is studied by using a new Monte Carlo Normal Mode Following (MC-NMF) technique, one applicable even without a target structure. The results demonstrate that the lowest-frequency normal mode (NM) at approximately 6.5 cm(-1) is the crucial mode that initiates dissociation. Perturbing the gA dimer in either direction along this NM leads to opposed, nearly rigid-body rotations of the gA monomers around the central pore axis. Tracking this NM by using the eigenvector-following technique reveals the channel's gating mechanism: dissociation via relative opposed monomer rotation and simultaneous lateral displacement. System evolution along the lowest-frequency eigenvector shows that the large-amplitude motions required for gating (dissociation) are not simple relative rigid-body motions of the monomers. Gating involves coupling intermonomer hydrogen bond breaking, backbone realignment, and relative monomer tilt with complex side chain reorganization at the intermonomer junction.
authors.affiliation: Department of Chemistry, MS-015 Brandeis University, P O Box 549110, Waltham, Massachusetts 02454, USA.
authors.forename: Gennady V
authors.initials: GV
authors.lastname: Miloshevsky
authors.forename: Peter C
authors.initials: PC
authors.lastname: Jordan
mesh_terms: D019281:Dimerization; D006096:Gramicidin / Q000737:chemistry*; D015640:Ion Channel Gating / Q000502:physiology*; D008958:Models, Molecular; D012399:Rotation
chemical_list: D006096:Gramicidin