• Bulletin of the Korean Chemical Society
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• v.32 no.4
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• pp.1241-1248
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• 2011

Three dimensional quantitative structure-activity relationships (3D-QSARs) between new thiosemicarbazone analogues (1-31) as a substrate molecule and their inhibitory activity against tyrosinase as a receptor were performed and discussed quantitatively using CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) methods. According to the optimized CoMSIA 2 model obtained from the above procedure, inhibitory activities were mainly dependent upon H-bond acceptor favored field (36.5%) of substrate molecules. The optimized CoMSIA 2 model, with the sensitivity of the perturbation and the prediction, produced by a progressive scrambling analysis was not dependent on chance correlation. From molecular docking studies, it is supposed that the inhibitory activation of the substrate molecules against tyrosinase (PDB code: 1WX2) would not take place via uncompetitive inhibition forming a chelate between copper atoms in the active site of tyrosinase and thiosemicarbazone moieties of the substrate molecules, but via competitive inhibition based on H-bonding.

• Bulletin of the Korean Chemical Society
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• v.32 no.7
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• pp.2433-2442
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• 2011

The three dimensional quantitative structure activity relationship (3D QSAR) models were developed using Comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA) and docking studies. The fit of Quinazolinone antifolates inside the active site of modeled bovine dihydrofolate reductase (DHFR) was assessed. Both ligand based (LB) and receptor based (RB) QSAR models were generated, these models showed good internal and external statistical reliability that is evident from the $q^2_{loo}$, $r^2_{ncv}$ and $r^2_{pred}$. The identified key features enabled us to design new Quinazolinone analogues as DHFR inhibitors. This study is a building bridge between docking studies of homology modeled bovine DHFR protein as well as ligand and target based 3D QSAR techniques of CoMFA and CoMSIA approaches.

• Journal of Integrative Natural Science
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• v.7 no.3
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• pp.159-165
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• 2014

Pyrazole, hydroxyimino, aldehyde and isoxazole derivatives exhibit a broad spectrum of biological activities such as antimicrobial, anti-inflammatory and antitumor activities. With growing application on their synthesis and bioactivity, chemists and biologists in recent years have considerable attention on the research of these derivatives. In the view of potential importance of these derivatives, we have crystallized few of the derivatives and its report has been published. The present study focuses on docking studies of these derivatives against Phospholipases $A_2$ enzyme. This enzymes has implicated as potential targets for anti-inflammatory drug design. co-crystal structure (PDB ID: 1POE) of $PLA_2$ deposited in Protein Data Bank has been retrieved for docking analysis. Docking studies using Schrodinger's GLIDE reveals that these derivatives shows better binding energy and score in the defined active site. These results may provide a guiding role to design a lead molecule which may reduce inflamation.

• CELLMED
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• v.3 no.2
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• pp.12.1-12.4
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• 2013

Identification of target protein is an important procedure in the course of drug discovery. Because of complexity, action mechanisms of herbal medicine are rather obscure, unlike small-molecular drugs. Inverse docking simulation is a reverse use of molecular docking involving multiple target searches for known chemical structure. This methodology can be applied in the field of target fishing and toxicity prediction for herbal compounds as well as known drug molecules. The aim of this review is to introduce a series of in silico works for predicting potential drug targets and side-effects based on inverse docking simulations.

• Bulletin of the Korean Chemical Society
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• v.28 no.12
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• pp.2248-2252
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• 2007

SOMT-9 is an O-methyltransferase that utilizes quercetin to produce 3'-methoxy quercetin. In order to determine which amino acids of SOMT-9 are important for this reaction and its regioselectivity, molecular docking experiments followed by site directed mutagenesis were performed. Molecular modeling and molecular docking experiments identified several amino acid residues involved in metal binding, AdoMet binding, and substrate binding. Site-directed mutagenesis showed that Asp188 is critical for metal binding and that Lys165 assists other metal binding residues in maintaining quercetin in the proper position during the reaction. In addition, Tyr207 was shown to play an important role in the determination of the regioselectivity and Met60 was shown to be involved in formation of the hydrophobic pocket necessary for substrate binding. The molecular modeling and docking experiments discussed in this study could be applicable to future research including prediction of substrate binding and regioselectivity of an enzyme.

• Bulletin of the Korean Chemical Society
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• v.29 no.8
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• pp.1479-1484
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• 2008

Protein tyrosine phosphatase (PTP) 1B is the superfamily of PTPs and a negative regulator of multiple receptor tyrosine kinases (RTKs). Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as a strategy for the treatment of type 2 diabetes and obesity. Recently, it has been reported that amentoflavone, a biflavonoid extracted from Selaginella tamariscina, inhibited PTP1B. In the present study, docking model between amentoflavone and PTP1B was determined using automated docking study. Based on this docking model and the interactions between the known inhibitors and PTP1B, we determined multiple pharmacophore maps which consisted of five features, two hydrogen bonding acceptors, two hydrogen bonding donors, and one lipophilic. Using receptor-oriented pharmacophore-based in silico screening, we searched the biflavonoid database including 40 naturally occurring biflavonoids. From these results, it can be proposed that two biflavonoids, sumaflavone and tetrahydroamentoflavone can be potent allosteric inhibitors, and the linkage at 5',8''-position of two flavones and a hydroxyl group at 4'-position are the critical factors for their allosteric inhibition. This study will be helpful to understand the mechanism of allosteric inhibition of PTP1B by biflavonoids and give insights to develop potent inhibitors of PTP1B.

• Bulletin of the Korean Chemical Society
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• v.27 no.2
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• pp.266-272
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• 2006

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed for 67 molecules of 2-amino-benzothiazole-6-anilide derivatives against lymphocyte-specific protein tyrosine kinase (P56 LCK). The molecular field analysis (MFA) and receptor surface analysis (RSA) were employed for QSAR studies and the predictive ability of the model was validated by 15 test set molecules. Structure-based investigations using molecular docking simulation were performed with the crystal structure of P56 LCK. Good correlation between predicted fitness scores versus observed activities was demonstrated. The results suggested that the nature of substitutions at the 2-amino and 6-anilide positions were crucial in enhancing the activity, thereby providing new guidelines for the design of novel P56 LCK inhibitors.

• Journal of Integrative Natural Science
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• v.8 no.3
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• pp.209-213
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• 2015

Influenza A virus (H1N1) causes and spreads infectious diseases and becomes a major health threat in humans. Among the subtypes of influenza virus, neuraminidase (NA) plays an important role in viral life cycle and becomes an attractive therapeutic target. Currently two NA inhibitors namely Zanamivir and Oseltamivir are available for treating infectious diseases. Recently five naturally derived polyphenols extracted from Phellinus baumii was reported as inhibitors against NA. Molecular docking is powerful tool in computer aided drug designing which aids in exploring and elucidating the properties of the molecules from their 3D structure. Hence, in the present study, molecular docking was carried out on reported polyphenols isolated from ethanolic extract of fruiting bodies of Phellinus baumii. The objective of this work was to study the interaction and to propose the binding mode of these compounds within the binding site of H1N1 neuraminidase. The results showed these compounds had better binding energy and H-bond interactions with the important active site residues of the receptor which authenticate these compounds contributes to inhibitory activity of neuraminidase to treat influenza infection.

• Journal of Integrative Natural Science
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• v.3 no.1
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• pp.49-53
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• 2010

Molecular docking is a critical event which mostly forms Van der waals complex in molecular recognition. Since the majority of developed drugs are small molecules, docking them into proteins has been a prime concern in drug discovery community. Since the binding pose space is too vast to cover completely, many search algorithms such as genetic algorithm, Monte Carlo, simulated annealing, distance geometry have been developed. Proper evaluation of the quality of binding is an essential problem. Scoring functions derived from force fields handle the ligand binding prediction with the use of potential energies and sometimes in combination with solvation and entropy contributions. Knowledge-based scoring functions are based on atom pair potentials derived from structural databases. Forces and potentials are collected from known protein-ligand complexes to get a score for their binding affinities (e.g. PME). Empirical scoring functions are derived from training sets of protein-ligand complexes with determined affinity data. Because non of any single scoring function performs generally better than others, some other approaches have been tried. Although numerous scoring functions have been developed to locate the correct binding poses, it still remains a major hurdle to derive an accurate scoring function for general targets. Recently, consensus scoring functions and target specific scoring functions have been studied to overcome the current limitations.

• Journal of Microbiology and Biotechnology
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• v.33 no.2
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• pp.268-276
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• 2023

Alkyl butyrate with fruity flavor is known as an important additive in the food industry. We synthesized various alkyl butyrates from various fatty alcohol and butyric acid using immobilized Rhodococcus cutinase (Rcut). Esterification reaction was performed in a non-aqueous system including heptane, isooctane, hexane, and cyclohexane. As a result of performing the alkyl butyrate synthesis reaction using alcohols of various chain lengths, it was found that the preference for the alcohol substrate had the following order: C6 > C4 > C8 > C10 > C2. Through molecular docking analysis, it was found that the greater the hydrophobicity of alcohol, the higher the accessibility to the active site of the enzyme. However, since the number of torsions increased as the chain length increased, it became difficult for the hydroxyl oxygen of the alcohol to access the ^γO of serine at the enzyme active site. These molecular docking results were consistent with substrate preference results of the Rcut enzyme. The Rcut maintained the synthesis efficiency at least for 5 days in isooctane solvent. We synthesized as much as 452 mM butyl butyrate by adding 100 mM substrate daily for 5 days and performing the reaction. These results show that Rcut is an efficient enzyme for producing alkyl butyrate used in the food industry.