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Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography
Published on: September 20, 2016
Probing non-peptide agonists binding at the human nociceptin/orphanin FQ receptor: a molecular modelling study
Matteo Gozzi1, Davide Malfacini2, Valentina Albanese3
1Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara 44121 Ferrara Italy antonella.ciancetta@unife.it.
Abstract:
The N/OFQ-NOP receptor is a fascinating peptidergic system with the potential to be exploited for the development of analgesic drugs devoid of side effects associated with classical opioid signalling modulation. To date, up to four X-ray and cryo-EM structures of the NOP receptor in complex with the endogenous peptide agonist N/OFQ and three small molecule antagonists have been solved and released. Despite the available structural information, the details of selective small molecule agonist binding to the NOP receptor in the active state remain elusive. In this study, by leveraging the available structural information and using N/OFQ(1-13)-NH2 as a reference compound, we developed a computational protocol based on docking followed by short molecular dynamics (MD) simulations that can suggest small molecule agonist binding modes at the NOP receptor that are reproducible and stable over time in the solvated membrane-embedded receptor active state and in agreement with known structure-activity relationship (SAR) data.
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