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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
Author(s) -
Pietra Francesco
Publication year - 2011
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201100060
Subject(s) - chemistry , ion channel , biophysics , docking (animal) , protein subunit , molecular dynamics , biochemistry , stereochemistry , biology , computational chemistry , receptor , medicine , nursing , gene
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 hASIC1aFMRFa 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.