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Homology modeling and molecular docking studies of Drosophila and Aedes sex peptide receptors

Kim, Jeong-hyun and Kim, Soo-Kyung and Lee, Jae-Hyuk and Kim, Young-Joon and Goddard, William A., III and Kim, Yong-Chul (2016) Homology modeling and molecular docking studies of Drosophila and Aedes sex peptide receptors. Journal of Molecular Graphics and Modelling, 66 . pp. 115-122. ISSN 1093-3263. https://resolver.caltech.edu/CaltechAUTHORS:20160412-130650913

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Abstract

The Drosophila melanogaster sex peptide receptor (DrmSPR), which is a G protein-coupled receptor (GPCR), is known as the specific receptor for sex peptide (SP). It is responsible for the reproductive behavior in the Drosophila model system; in particular, it is involved in the post-mating responses such as the increase in egg-laying ability and decrease in receptivity in females. In a previous study, we discovered a small molecule agonist of DrmSPR for the first time, which could not, however, activate Aedes aegypti SPR (AedesSPR). To investigate the binding mechanism of the small molecule agonist of DrmSPR, the ensemble structures of low-lying packing structures of DrmSPR and AedesSPR were assembled using the GEnSeMBLE (GPCR Ensemble of Structures in Membrane BiLayer Environment) method. The generated homology models exhibited the typical pattern of inter-helical interactions of the class A GPCRs. The docking experiments of the small molecule agonist suggest that Tyr^(5.35) and Phe^(2.67) residues may be involved in a hydrophobic interaction and that Ser^(3.25) forms a hydrogen bond with the agonist. Additionally, we found that the docking results were consistent with the experimental data of the reference compounds with variable agonistic activities. Moreover, a potential distinction of the putative binding sites in two GPCR models of DrmSPR and AedesSPR, which was determined in this study, can explain the selective action of the agonist for DrmSPR but not for AedesSPR.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.jmgm.2016.03.014DOIArticle
http://www.sciencedirect.com/science/article/pii/S1093326316300481PublisherArticle
ORCID:
AuthorORCID
Kim, Soo-Kyung0000-0002-4498-5441
Goddard, William A., III0000-0003-0097-5716
Additional Information:© 2016 Elsevier Inc. Received 21 October 2015, Revised 7 March 2016, Accepted 24 March 2016, Available online 25 March 2016.
Subject Keywords:Drosophila sex peptide receptor; G protein-coupled receptor; GPCR modeling; Docking; Binding site prediction; BiHelix/SuperBiHelix; GEnSeMBLE; Pyrazolodiazepine
Record Number:CaltechAUTHORS:20160412-130650913
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160412-130650913
Official Citation:Jeong-hyun Kim, Soo-Kyung Kim, Jae-Hyuk Lee, Young-Joon Kim, William A. Goddard III, Yong-Chul Kim, Homology modeling and molecular docking studies of Drosophila and Aedes sex peptide receptors, Journal of Molecular Graphics and Modelling, Volume 66, May 2016, Pages 115-122, ISSN 1093-3263, http://dx.doi.org/10.1016/j.jmgm.2016.03.014. (http://www.sciencedirect.com/science/article/pii/S1093326316300481)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66088
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:12 Apr 2016 21:36
Last Modified:09 Mar 2020 13:18

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