On the putative binding site of RFamide-family neuropeptides from the western Atlantic clam Sunray Venus and cephalopods on acid-sensing ion channels. An automated docking and molecular-dynamics study with hASIC1a homology model

Investigated here are interactions of C-terminal amidated peptides with the hASIC1a acid-sensing ion channel. The peptides comprise endogenous FMRFa, present in the western Atlantic clam Sunray Venus, and FIRFa, present in cephalopods, as well as non-endogenous ones for comparison. The interaction is investigated by automated docking. The resulting key hASIC1a-FMRFa complex, set in a lipidic POPC (=1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) membrane surrounded by H(2) O and Na(+) -neutralized, was also investigated by molecular dynamics. It was observed that all investigated peptides become encapsulated into the ion channel, on one side by the thumb and finger of a subunit, and, on the opposite side, by the knuckle and β-ball of a second subunit. The third subunit is not involved. This is much the same binding site that was disclosed previously by both a similar computational approach, and electrophysiological and binding experiments for the hASIC1a ion channel-blocker tarantula toxin PCTX1. This paves the way to a better understanding of the role of these peptides in invertebrates.