Abstract
The development of physiologically active semiochemicals is largely limited by the labor-consuming searching process. How to screen active semiochemicals efficiently is of significance to the extension of behavior regulation in pest control. Here pharmacophore modeling and shape-based virtual screening were combined to predict candidate ligands for Cydia pomonella pheromone binding protein 1 (CpomPBP1). Out of the predicted compounds, ETrME displayed the highest affinity to CpomPBP1. Further studies on the interaction between CpomPBP1 and ETrME, not only depicted the binding mode, but also revealed residues providing negative and positive contributions to the ETrME binding. Moreover, key residues involved in interacting with ETrME of CpomPBP1 were determined as well. These findings were significant to providing insights for the future searching and optimization of active semiochemicals.
Highlights
Chemical communication in insects takes place by perceiving a myriad of semiochemicals in the olfaction system[1,2,3,4]
CpomPBP1-Codlemone complex was constructed based on the homology 3D model of CpomPBP1 (Figure S1a), key interactions between Codlemone and CpomPBP1 derived from the constructed complex were transformed into a hypothesis of pharmacophore by LigandScout4.09
Several excluded volumes localized in the space regions where the backbones or sidechains of residues lie were automatically generated in the model, reflecting that these regions were inaccessible to any potential ligand due to possible steric restrictions
Summary
Chemical communication in insects takes place by perceiving a myriad of semiochemicals in the olfaction system[1,2,3,4]. Leal in 2005 advanced the notion of “reverse chemical ecology”, a new concept for semiochemicals discovery based on the binding ability of olfaction related proteins rather than the bioassays of insect behaviors[11]. What should be confessed is that searching for potentially active semiochemicals based on in vitro binding studies with ORs is technically infeasible, especially when considering that functional expression of ORs is far from easy[11,16]. The aim of this study is to discover potentially active semiochemicals for Cydia pomonella through pharmacophore-based virtual screening. Pharmacophore-based virtual screening is used in combination with other three methods including Gaussians molecule shape similarity, binding affinity calculation and in vitro binding assay to discover potentially active semiochemicals for Cydia pomonella. Pharmacophore-based virtual screening provides a convenient way to search large chemical database and increases the chance of target hitting. What’s more, the revelation of binding mode (driving forces of binding, key residues, etc.) is of guiding importance to the rational design of novel active semiochemicals
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: 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.
