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Prediction of the ligand-binding modes of various molecules to the molting hormone receptor using docking simulation

A session at JCUP IV

Thursday 6th June, 2013

2:30pm to 3:00pm (CJT)

Insect molting is initiated by interaction of the molting hormone (20-hydroxyecdysone: 20E) with the ecdysone receptor (EcR). Thus, compounds that modulate the 20E-EcR interaction are able to interrupt insect molting and therefore may have useful insecticidal activity. Diacylhydrazines (DAHs) have been found to disrupt the 20E-EcR interaction and five DAHs, including tebufenozide and chromafenozide, are currently in use as insecticides. Most of them are very toxic to Lepidoptera but inactive or very weakly active against other insect orders such as Diptera and Coleoptera. This order-specific toxicity of DAHs is caused by differences in their binding affinity to the EcRs in the different insect species. The three dimensional structures of the ligand binding domains (LBDs) of EcR of Heliothis virescens (HvEcR) complexed with ponasterone A (PonA) and 20E have been solved crystallographically. Furthermore, EcR bound to a DAH (BYI06830, a chromafenozide analog) has also been solved, and comparison of the structures found that PonA and DAHs partially overlap when bound to the LBD of EcR.

In this study, homology models of EcR-LBDs from various insect species are built based on EcR crystal structures, and the binding modes of various ligands are investigated using ligand-receptor docking simulations to investigate species selectivity and affinity.

The relative affinities of some ecdysteroids and a set of plant steroid hormones is successfully rationalized based on analysis of their docked poses, as well as the species selectivity of a set of DAHs. Docking simulations are also used successfully to understand outliers in a previously developed QSAR for DAHs.

About the speaker

This person is speaking at this event.
Yoshiaki Nakagawa

Kyoto University - Professor bio from LinkedIn

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JCUP IV

Japan Japan, Tokyo

6th7th June 2013

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When

Time 2:30pm3:00pm CJT

Date Thu 6th June 2013

Where

Ohtemachi SunSky Room, Asahi Seimei Ohtemachi Building

Short URL

lanyrd.com/schymq

Official event site

www.eyesopen.com/events/jcup4

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