• Journal of Korean Society for Atmospheric Environment
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• v.29 no.4
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• pp.459-476
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• 2013

Receptor models have been rapidly developed to manage the ambient air quality and to establish effective emission reduction strategies. The models are used to identify various emission sources and apportion quantitatively the ambient pollutant mass based on various measured physico-chemical properties of the air pollutants at the receptor site. Many types of receptor models have been applied to estimate source contributions since those provide fundamental information when establishing reasonable environmental policies in Korea and Foreign countries. In this paper, we will introduce the basic concept and principal of the receptor model, various types of existing models with discussing strong and weak points for each model, and performance procedure of PMF model as the most popular model in the world. Further the trends of receptor modeling studies in Korea and other countries were provided. Finally, the improvement directions of the modeling works for the national and local air quality management were suggested in this paper.

• Journal of Integrative Natural Science
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• v.6 no.1
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• pp.16-20
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• 2013

G-protein-coupled receptor (GPCR) superfamily is the largest known receptor family, characterized by seven transmembrane domains and considered to be an important drug target. In this study we focused on an orphan GPCR termed as GPR18. As there is no X-ray crystal structure has been reported for this receptor, we report on a homology model of GPR18. Template structure with high homology was used for modeling and ten models were developed. A model was selected and refined by energy minimization. The selected model was further validated using various parameters. Our results could be a starting point for further structure based drug design.

• Journal of Integrative Natural Science
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• v.5 no.1
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• pp.32-37
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• 2012

Chemokine receptor antagonists have potential applications in field of drug discovery. Although the chemokine receptors are G-protein-coupled receptors, their cognate ligands are small proteins (8 to 12 kDa), and so inhibiting the ligand/receptor interaction has been challenging. The application of structure-based in-silico methods to drug discovery is still considered a major challenge, especially when the x-ray structure of the target protein is unknown. Such is the case with human CCR2 and CCR5, the most important members of the chemokine receptor family and also a potential drug target. Herein, we review the success stories of combined receptor modeling/mutagenesis approach to probe the allosteric nature of chemokine receptor binding by small molecule antagonists for CCR2 and CCR5 using Rhodopsin as template. We also urged the importance of recently available ${\beta}2$-andrenergic receptor as an alternate template to guide mutagenesis. The results demonstrate the usefulness and robustness of in-silico 3D models. These models could also be useful for the design of novel and potent CCR2 and CCR5 antagonists using structure based drug design.

• Journal of Integrative Natural Science
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• v.8 no.1
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• pp.75-79
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• 2015

Thromboxane A2 receptors (TXA2-R) are the G protein coupled receptors localized on cell membranes and intracellular structures and play pathophysiological role in various thrombosis/hemostasis, modulation of the immune response, acute myocardial infarction, inflammatory lung disease, hypertension and nephrotic disease. TXA2 receptor antagonists have been evaluated as potential therapeutic agents for asthma, thrombosis and hypertension. The role of TXA2 in wide spectrum of diseases makes this as an important drug target. Hence in the present study, homology modeling of TXA2 receptor was performed using the crystal structure of squid rhodopsin and night blindness causing G90D rhodopsin. 20 models were generated using single and multiple templates based approaches and the best model was selected based on the validation result. We found that multiple template based approach have given better accuracy. The generated structures can be used in future for further binding site and docking analysis.

• Journal of Integrative Natural Science
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• v.7 no.4
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• pp.234-240
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• 2014

C-C chemokine receptor type 4 (CCR4) is a chemokine receptor with seven transmembrane helices and it belongs to the GPCR family. It plays an important role in asthma, lung disease, atopic dermatitis, allergic bronchopulmonary aspergillosis, cancer, inflammatory bowel disease, the mosquito-borne tropical diseases, such as dengue fever and allergic rhinitis. Because of its role in wide spectrum of disease processes, CCR4 is considered to be an important drug target. Three dimensional structure of the protein is essential to determine the functions. In the present study homology modeling of human CCR4 was performed based on crystal structure of CCR5 chemokine receptor. The generated models were validated using various parameters. Among the generated homology models the best one is selected based on validation result. The model can be used for performing further docking studies to identifying the critical interacting residues.

• Journal of Integrative Natural Science
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• v.8 no.3
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• pp.164-175
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• 2015

CXCR3 is a C-X-C chemokine receptor type 3 also known as GPR9 and CD183. CXCR3 is a G-Protein coupled chemokine receptor which interacts with three endogenous interferon inducible chemokine's (CXCL9, CXCL10 and CXCL11) and is proved to play a vital role in the Th1 inflammatory responses. CXCR3 has been implicated to be associated with various disease conditions like inflammatory diseases, autoimmune diseases, type I diabetes and acute cardiac allograft rejection. Therefore CXCR3 receptor is found to be an attractive therapeutic target for the treatment of inflammatory diseases. Inorder to decipher the biological function of a CXCR3, 3D structure is of much important but the crystal structure for CXCR3 has not yet been resolved. Hence, in the current study Homology modeling of CXCR3 was performed against various templates and validated using different parameters to suggest the best model for CXCR3. The reported best model can be used for further studies such as docking to identify the important binding site residues.

• Proceeding of EDISON Challenge
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• 2013.04a
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• pp.13-24
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• 2013

Dopamine agonists and antagonists and its receptor play a critical role in the information transfer in the nervous system, and dopamine receptor-ligands interactions are deeply related to Parkinson's disease, schizophrenia and some other mental diseases. However, the only experimental 3D structure available for dopamine receptors is human D3 dopamine receptor. Therefore, it is important to create model of subtype dopamine receptor-ligands interactions. We report here the 3D structures of the human D1 and D2 dopamine receptor predicted by using GalaxyTBM, and its predicted binding site determined by using GalaxyDock. The highly conserved Asp on TM 3 and Phe on TM 6 have critical role in ligand binding. Also, highly conserved serines on TM 5 are essential for binding agonists and some kinds of antagonists. We identify differences between binding sites of agonists and antagonists of human D1 and D2 dopamine receptor, and find the reasons of selective binding of antagonists.

• Journal of Integrative Natural Science
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• v.8 no.1
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• pp.13-18
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• 2015

Cysteinyl leukotrienes are inflammatory mediators having important role in pathophysiological conditions such as asthma, allergic rhinitis and have been implicated in a number of inflammatory conditions including cardiovascular and gastrointestinal diseases. Most of the disease regulatory actions of the CysLTs are mediated through CysLT1 receptor. Hence in the present study, homology modeling of CysLT1 was performed because the availability of 3D structure would enhance the development of new drugs for inflammatory diseases. However the templates identified have low sequence identity which increases the complexity of modeling. Hence, homology modeling was performed using single template, multiple templates and also using threading I-TASSER server. The best model was selected based on the validation of the generated models using Ramachandran and ERRAT plot. The model developed could be useful for identifying crucial residues and docking study.

• Proceedings of the Korea Air Pollution Research Association Conference
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• 1994.10a
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• pp.109-109
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• 1994

• Bulletin of the Korean Chemical Society
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• v.32 no.6
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• pp.2008-2014
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• 2011

Serotonin or 5-hydroxytryptamine subtype 2C ($5-HT_{2C}$) receptor belongs to class A amine subfamily of G-protein-coupled receptor (GPCR) super family and its ligands has therapeutic promise as anti-depressant and -obesity agents. So far, bovine rhodopsin from class A opsin subfamily was the mostly used X-ray crystal template to model this receptor. Here, we explained homology model using beta 2 adrenergic receptor (${\beta}$2AR), the model was energetically minimized and validated by flexible ligand docking with known agonists and antagonists. In the active site Asp134, Ser138 of transmembrane 3 (TM3), Arg195 of extracellular loop 2 (ECL2) and Tyr358 of TM7 were found as important residues to interact with agonists. In addition to these, V208 of ECL2 and N351 of TM7 was found to interact with antagonists. Several conserved residues including Trp324, Phe327 and Phe328 were also found to contribute hydrophobic interaction. The predicted ligand binding mode is in good agreement with published mutagenesis and homology model data. This new template derived homology model can be useful for further virtual screening based lead identification.