The 5-amino acid N-terminal extension of non-sulfated drosulfakinin II is a unique target to generate novel agonists

Structure-Activity Relationship Data and Ligand-Receptor Interactions Identify Novel Agonists Consistent with Sulfakinin Tissue-Specific Signaling in Drosophila Melanogaster Heart

“…To that end, our previous SAR analysis of the extension on gut motility across three developmental stages identified a super agonist and a protean agonist. Furthermore, ligand-receptor interactions are consistent with nsDSK II acting through DSK-R2 in gut [10]. While the nsDSK II SAR for gut motility and locomotion is reported [10], it remains unknown in heart.…”

“…Furthermore, ligand-receptor interactions are consistent with nsDSK II acting through DSK-R2 in gut [10]. While the nsDSK II SAR for gut motility and locomotion is reported [10], it remains unknown in heart. We predicted the extension SAR is tissue specific consistent with cardiac CCK structure activity and signaling being different from gut [11,12].…”

“…Three-dimensional receptor structures of DSK-R1 and DSK-R2 and ligand modeling were previously reported [10,[14][15][16]. The primary sequences [7] were submitted to I-TASSER [17,18] and refined in Mod Refiner [19] after which the receptor structures were viewed in PyMOL (Schrödinger, LLC).…”

“…To prepare for docking, extracellular loops (ECLs) and tails were removed and a binding pocket of less than 27000 cubic angstroms was defined using AutoDock Tools-1.5.6. Ligand models were built in Py-MOL for docking in AutoDockTools [10,[14][15][16]20,21].…”

“…PyMOL and the molecular docking software AutoDock Vina were used to dock ligands to DSK-R1 and DSK-R2 to predict contact sites as previously reported [10,[14][15][16]. Physicochemical properties, type and number, proximity of ligand-receptor contacts, and pose overlap were used to evaluate the one group most likely to represent docking.…”