• Reproductive and Developmental Biology
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• v.34 no.3
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• pp.117-122
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• 2010

To search the potent pig pheromonal odorants through receptor-based approach methods, molecular dockings between 680 Flavomets as substrate molecule and pig odorants binding proteins OBP (1HQP) and PBP (1GM6) as receptor, and QSPR (quantitative structure-property relationship) analyses from physico-chemical parameters of Flavomets and their docking scores (DS) were performed and discussed quantitatively. From the basis on the findings, the optimal value $(MSA)_{opt.}=407.595\;{\AA}^2$ of MSA (molecular surface area; ${\AA}$), and RB (number of rotational bond) had the Flavomets will be able to increase DS. Therefore, it is expected that the stearyl alcohol from DS and H-bond type between substrate and receptor would be shows the character as potent pig pheromonal odorant.

• Journal of Radiation Protection and Research
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• v.35 no.1
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• pp.6-11
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• 2010

Embodying the safety of radioactive waste disposal requires the relevant safety criteria and the corresponding stylized methods to demonstrate its compliance with the criteria. This paper proposes a conceptual model of risk-based safety evaluation for integrating complex potential radiation exposure situations in radioactive waste disposal. For demonstrating compliance with a risk constraint, the approach deals with important exposure scenarios from the viewpoint of the receptor to estimate the resulting risk. For respective exposure situations, it considers the occurrence probabilities of the relevant exposure scenarios as their probability of giving rise to doses to estimate the total risk to a representative person by aggregating the respective risks. In this model, an exposure scenario is simply constructed with three components:radionuclide release, radionuclide migration and environment contamination, and interaction between the contaminated media and the receptor. A set of exposure scenarios and the representative person are established from reasonable combinations of the components, based on a balance of their occurrence probabilities and the consequences. In addition, the probability of an exposure scenario is estimated on the assumption that the initiating external factors influence release mechanisms and transport pathways, and its effect on the interaction between the environment and the receptor may be covered in terms of the representative person. This integrated approach enables a systematic risk assessment for complex exposure situations of radioactive waste disposal and facilitates the evaluation of compliance with risk constraints.

• Journal of Integrative Natural Science
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• v.16 no.1
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• pp.33-38
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• 2023

The follicle stimulating hormone receptor (FSHR) is a glycoprotein hormone, that belongs to the GPCR superfamily. FSHR plays a major role in reproduction. The aberrant activation of FHS receptor leads to infertility and several reproductive disorders. The recently recognized roles of the FSHR in diverse extragonadal tissues is also closely related to Alzheimer's disease and cancers. Analysing the structural characteristics of the receptor is important in understanding the pathophysiology of diseases associated with the receptor. In this present study, homology modelling of FSHR-TM domain was developed using four different templates. Totally 20 models were developed using single template-based approach and selected three based on the validation of RC plot, RMSD, ProSA, QMEAN and ERRAT values. The developed models would be useful for further research on the structural characteristics and binding characteristics of the FSHR-TM domain.

• 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.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.

• Molecules and Cells
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• v.28 no.3
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• pp.195-200
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• 2009

Protein tyrosine kinases (PTKs) play a central role in the modulation of a wide variety of cellular events such as differentiation, proliferation and metabolism, and their unregulated activation can lead to various diseases including cancer and diabetes. PTKs represent a diverse family of proteins including both receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (NRTKs). Due to the diversity and important cellular roles of PTKs, accurate classification methods are required to better understand and differentiate different PTKs. In addition, PTKs have become important targets for drugs, providing a further need to develop novel methods to accurately classify this set of important biological molecules. Here, we introduce a novel statistical model for the classification of PTKs that is based on their structural features. The approach allows for both the recognition of PTKs and the classification of RTKs into their subfamilies. This novel approach had an overall accuracy of 98.5% for the identification of PTKs, and 99.3% for the classification of RTKs.

• Journal of Integrative Natural Science
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• v.10 no.4
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• pp.209-215
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• 2017

CXC chemokine receptor 2 (CXCR2) is a prominent chemokine receptor on neutrophils. CXCR2 antagonist may reduce the neutrophil chemotaxis and alter the inflammatory response because the neutrophilic inflammation in the lung diseases is found to be largely regulated through CXCR2 receptor. Hence, in the present study, Topomer based Comparative Molecular Field Analysis (Topomer CoMFA) was performed on a series of CXCR2 antagonist named pyrimidine-5-carbonitrile-6-alkyl derivatives. The best Topomer COMFA model was obtained with significant cross-validated correlation coefficient ($q^2$ = 0.487) and non cross-validated correlation coefficients ($r^2$ = 0.980). The model was evaluated with six external test compounds and its $r^2{_{pred}}$ was found to be 0.616. The steric and electrostatic contribution map show that presence of bulkier and electropositive group around cyclopropyl ring may contribute more for improving the biological activities of these compounds. The generated Topomer CoMFA model could be helpful for future design of novel and structurally related CXCR2 antagonists.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.469-473
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• 2009

Induced activation of the gamma-aminobutyric $acid_A$ ($GABA_A$) receptor in the retina of goldfish caused the fish to rotate in the opposite direction to that of the spinning pattern during an optomotor response (OMR) measurement. Muscimol, a $GABA_A$ receptor agonist, modified OMR in a concentration-dependent manner. The $GABA_B$ receptor agonist baclofen and $GABA_C$ receptor agonist CACA did not affect OMR. The observed modifications in OMR included decreased anterograde rotation $(0.01\sim0.03\;{\mu}M)$, coexistence of retrograde rotation and decreased anterograde rotation $(0.1\sim30\;{\mu}M)$ and only retrograde rotation $(100\;{\mu}M\sim1\;mM)$. In contrast, the $GABA_A$ receptor antagonist bicuculline blocked muscimol-induced retrograde rotation. Based on these results, we inferred that the coding inducing retrograde movement of the goldfish retina is essentially associated with the GABAA receptor-related visual pathway. Furthermore, from our novel approach using observations of goldfish behavior the induced discrete snapshot duration was approximately 573 ms when the fish were under the influence of muscimol.

• Journal of Plant Biotechnology
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• v.45 no.4
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• pp.315-321
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• 2018

Molecular and functional characterization of proteins and their levels is of great interest in understanding the mechanism of diverse cellular processes. In this study, we report on the convenient Escherichia coli-based protein expression system that allows recombinant of soluble proteins expression and cytosolic domain of membrane-localised kinases, followed by the detection of autophosphorylation activity in protein kinases. This approach is applied to regulatory proteins of Arabidopsis thaliana, including 14-3-3, calmodulin, calcium-dependent protein kinase, TERMINAL FLOWER 1(TFL1), FLOWERING LOCUS T (FT), receptor-like cytoplasmic kinase and cytoplasmic domain of leucine-rich repeat-receptor like kinase proteins. Our Western blot analysis which uses phospho-specific antibodies showed that five putative LRR-RLKs and two putative RLCKs have autophosphorylation activity in vitro on threonine and/or tyrosine residue(s), suggesting their potential role in signal transduction pathways. Our findings were also discussed in the broader context of recombinant expression and biochemical analysis of soluble and membrane-localised receptor kinases in microbial systems.

• Journal of Integrative Natural Science
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• v.3 no.3
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• pp.162-167
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• 2010

A pseudoreceptor combines structure-based and ligand-based techniques to represent a unifying concept for both receptor mapping and ligand matching. In this molecular modeling approach, there are opportunities to construct the pseudoreceptor models using a set of small molecules. To build a reliable pseudoreceptor model, we need a set of ligand molecules with known affinity (biological activity) to generate 3D bioactive conformation for each of these ligand molecules. Several software packages are available to generate a pseudoreceptor model and this can provide an entry point for structure based drug discovery in cases where receptor structure information is not available. In this review, we presented the concept of pseudoreceptor, as well as discussed about various software packages available to generate a pseudoreceptor model.