A MOLECULAR-DYNAMICS STUDY OF GATING IN DIOXOLANE-LINKED GRAMICIDIN-ACHANNELS

The gating transition of the RR and SS dioxolane ring-linked gramicidi n A channels were studied with molecular dynamics simulations using a detailed atomic model. It was found that the probable reaction path, d escribing the transition of the ring from the exterior to the interior of the channel where it blocked the permeation pathway, involved seve ral steps including the isomerization of the transpeptide plane dihedr al angle of Val(1). Reaction coordinates along this pathway were defin ed, and the transition rates between the stable conformers were calcul ated. It was found, in good accord with experimental observations, tha t the calculated blocking rate for the RR-linked channel was 280/s wit h a mean blocking time of 0.04 ms, whereas such blocking did not occur in the case of the SS-linked channel. An important observation is tha t the resulting lifetime for the blocked state of the RR-linked channe l was in good accord with the experimental observations only when the calculations were performed in the presence of a potassium ion inside the channel.