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Homology modeling, agonist binding site identification, and docking in octopamine receptor of Periplaneta americana.
Comput Biol Chem. 2008 Jun; 32(3):185-90.CB

Abstract

AY333178 (from Periplaneta americana, 628 AAs) was selected as a target octopamine receptor (OAR) class OAR2 for this study using Discovery Studio (DS Modeling1.1/1.2, Accelrys Inc.). Blast similarity search was performed and identified that AY333178 contains N-terminal domain of GPCR. Based upon Blast and Pfam results, Rhodopsin 1U19 (protein data bank) was considered as an ideal homologue and used as a template for homology modeling due to its higher X-ray resolution at 2.2A. Sequence alignment between AY333178 and 1U19 was done using Align123 followed by a manual modification. The final alignment was carefully evaluated and evidenced to be matching the conserved residue data for class A GPCR fairly well. The 3D model of AY333178 was generated with MODELER, and further refined using CHARMm. Superimposition of the model was done over the template 1U19. Two fairly consistent profiles were observed demonstrating AY333178 model was reasonable and could be employed for the further docking study. Agonist docking into OAR2 model was done using LigandFit. The superimposition of two top poses of representative agonists was performed with a soft surface generated. Those models are considered to be used in designing new leads for hopefully more active compounds. Further research on the comparison of models for the agonists may elucidate the mechanisms of OAR2-ligand interactions.

Authors+Show Affiliations

Division of Bioresource and Bioenvironmental Sciences, Graduate School, Kyushu University, Fukuoka 812-8581, Japan. ahirasim@agr.kyushu-u.ac.jpNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18430608

Citation

Hirashima, Akinori, and Hongwei Huang. "Homology Modeling, Agonist Binding Site Identification, and Docking in Octopamine Receptor of Periplaneta Americana." Computational Biology and Chemistry, vol. 32, no. 3, 2008, pp. 185-90.
Hirashima A, Huang H. Homology modeling, agonist binding site identification, and docking in octopamine receptor of Periplaneta americana. Comput Biol Chem. 2008;32(3):185-90.
Hirashima, A., & Huang, H. (2008). Homology modeling, agonist binding site identification, and docking in octopamine receptor of Periplaneta americana. Computational Biology and Chemistry, 32(3), 185-90. https://doi.org/10.1016/j.compbiolchem.2008.03.001
Hirashima A, Huang H. Homology Modeling, Agonist Binding Site Identification, and Docking in Octopamine Receptor of Periplaneta Americana. Comput Biol Chem. 2008;32(3):185-90. PubMed PMID: 18430608.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Homology modeling, agonist binding site identification, and docking in octopamine receptor of Periplaneta americana. AU - Hirashima,Akinori, AU - Huang,Hongwei, Y1 - 2008/03/16/ PY - 2007/10/16/received PY - 2008/03/10/accepted PY - 2008/4/24/pubmed PY - 2008/7/31/medline PY - 2008/4/24/entrez SP - 185 EP - 90 JF - Computational biology and chemistry JO - Comput Biol Chem VL - 32 IS - 3 N2 - AY333178 (from Periplaneta americana, 628 AAs) was selected as a target octopamine receptor (OAR) class OAR2 for this study using Discovery Studio (DS Modeling1.1/1.2, Accelrys Inc.). Blast similarity search was performed and identified that AY333178 contains N-terminal domain of GPCR. Based upon Blast and Pfam results, Rhodopsin 1U19 (protein data bank) was considered as an ideal homologue and used as a template for homology modeling due to its higher X-ray resolution at 2.2A. Sequence alignment between AY333178 and 1U19 was done using Align123 followed by a manual modification. The final alignment was carefully evaluated and evidenced to be matching the conserved residue data for class A GPCR fairly well. The 3D model of AY333178 was generated with MODELER, and further refined using CHARMm. Superimposition of the model was done over the template 1U19. Two fairly consistent profiles were observed demonstrating AY333178 model was reasonable and could be employed for the further docking study. Agonist docking into OAR2 model was done using LigandFit. The superimposition of two top poses of representative agonists was performed with a soft surface generated. Those models are considered to be used in designing new leads for hopefully more active compounds. Further research on the comparison of models for the agonists may elucidate the mechanisms of OAR2-ligand interactions. SN - 1476-9271 UR - https://www.unboundmedicine.com/medline/citation/18430608/Homology_modeling_agonist_binding_site_identification_and_docking_in_octopamine_receptor_of_Periplaneta_americana_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1476-9271(08)00025-X DB - PRIME DP - Unbound Medicine ER -