Un-gating and allosteric modulation of a pentameric ligand-gated ion channel captured by molecular dynamics
Fig 8
Receptor twisting versus blooming for the four simulations of GluCl.
The simulations of the end points of gating in green (resting) and red (active) sample values of the twisting and blooming reaction coordinates that are consistent with the X-ray structures of GluCl apo (green diamond) and GluCl with IVM bound (red diamond), respectively. When IVM is removed, a striking evolution of both twisting (from 15° to 22°) and blooming (from 8° to 10°) angles is observed. When only L-Glu is bound (orange) the receptor is partially twisted (τ of 17°) and contracted (θp of 8°). Isocontour lines on the relaxation of GluCl with IVM removed (blue) are used as visual guidelines to show the existence of a kinetic intermediate sampled in the early stages of the simulation. On the right-hand side, representative structures for the four simulations are shown using the same color code. The structural comparison illustrate the global character of the gating isomerization.