Abstract
Insect Ryanodine receptor (RyR) is an intracellular calcium release channels that play a key role in calcium signaling in numerous cell types. Targeting Ryanodine receptor is considered as efficient treatment option for the control of diamondback moth, Plutella xylostella, an important pest of cruciferous crops. The present study was carried out to identify potential RyR modulators through pharmacophore modeling and virtual screening. A total of 23 experimentally proven activators of RyR were used in the development of pharmacophore model. The resulting pharmacophore consisted of one hydrogen bond acceptor site (A), one hydrophobic feature site (H) and three aromatic ring sites (R). The model AHRRR was used as a query to find effective activators through database screening and AHRRR was validated to check its reliability using enrichment calculations. ADME properties were predicted to confirm the safety profile of the identified virtual hits. Furthermore, a structural modeling approach combining computational mutagenesis, induced fit docking, MM/GBSA and DFT calculations was used to evaluate the binding mode and structural basis of the two activators screened from pharmacophore-based virtual screening. Thus, the results could provide more knowledge on the activation of RyR and helpful in the development of more potent insecticides to overcome diamide insecticide resistance.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.