• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2005년도 BIOINFO 2005
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• pp.35-40
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• 2005

Interaction of twelve erythromycin A analogues with 50S ribosomal subunit were studied employing AutoDock 3.0.5. Results showed that all active macrolides bound at the same binding site with erythromycin A in contrast to the inactive analogues which bound at location slightly different than erythromycin A. The binding site showed consistency with the X-ray data from the perspectives of hydrogen bonding and hydrophobic interactions formed by erythromycins, roxithromycin, azithromycin, cethromycin and telithromycin with the ribosome. The inactive derivatives of erythromycin A anhydride showed higher binding free energy, while 5-desosaminyl erythronolides A and B even though having quiet similar values of binding free energy with the active analogues, docked at binding sites which are quiet different than the active analogues. These results suggest the molecular docking technique can be used in predicting the binding of erythromycin A analogues to their ribosomal target.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3119-3121
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• 2012

Non-small-cell lung cancer (NSCLC) is a leading cause of cancer deaths worldwide. Crizotinib has been approved by the U.S. Food and Drug Administration for the treatment of patients with advanced NSCLC. However, understanding of mechanisms of action is still limited. In our studies, we confirmed crizotinib-induced apoptosis in A549 lung cancer cells. In order to assess mechanisms, small molecular docking technology was used as a preliminary simulation of signaling pathways. Interesting, our results of experiments were consistent with the results of computer simulation. This indicates that small molecular docking technology should find wide use for its reliability and convenience.

• 통합자연과학논문집
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• 제9권1호
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• pp.41-61
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• 2016

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Phosphoinositide 3-kinases (PI3Ks) play important role in Non-Small Cell Lung Cancer. PI3Ks constitute a lipid kinase family which modulates the function of numerous substrates involved in the regulation of cell survival, cell cycle progression and cellular growth. Herein, we describe the ligand based pharmacophore combined with molecular docking studies methods to identify new potent PI3K inhibitors. Several pharmacophore models were generated and validated by Guner-Henry scoring Method. The best models were utilized as 3D pharmacophore query to screen against ZINC database (Chemical and Natural) and the retrieved hits were further validated by fitness score, Lipinski's rule of five. Finally four compounds were found to have good potential and they may act as novel lead compounds for PI3K inhibitor designing.

• 통합자연과학논문집
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• 제6권4호
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• pp.205-210
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• 2013

Human P-gp is a protein responsible for the multidrug resistance (MDR) and causes failure of cancer chemotherapy. Till date no X-ray crystal structure is reported for this membrane protein, which hampers active research in the field. We performed homology modeling to develop three dimensional (3D) model of P-gp, and docking studies of the verapamil and curcumin have been performed to gain insight into the interaction mechanism between inhibitors and P-gp. It was identified that the inhibitors docked into the upper part of P-gp and interacted through the hydrophobic interactions.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.65.2-65.2
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• 2003

88 selective COX-2 inhibitors belonging to three chemical classes (triaryl rings, diaryl cycloalkanopyrazoles, and diphenyl hydrazides) were studied using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Partial least squares analysis produced statistically significant models with q values of 0.84 and 0.79 for CoMFA and CoMSIA, respectively. The key spatial properties were detected by careful analysis of the isocontour maps. The binding energies calculated from flexible docking correlated with inhibitory activities by the least-squares fit method. (omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.180.2-180.2
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• 2003

Cathepsin K, a cysteine protease of the papain superfamily, is predominantly expressed in osteoclasts and has been postulated as a target for the treatment of osteoporosis. Crystallographic and structure-activity studies on a series of azepanone-based diamino and acyclic ketone derivative inhibitors of cathepsin K have led to the design and identification. X-ray structure of the cysteine protease cathepsin K (1NL6) co-crystalized with an inhibitor with 2.8${\AA}$ resolution was used to predict the protein-ligand interactions and to estimate the binding affinity from the docking score by FlexX module. (omitted)

• 통합자연과학논문집
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• 제4권3호
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• pp.202-209
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• 2011

Tuberculosis is a major health problem in humans because of its multidrug resistance and discovering new treatments for this disease is urgently required. The synthesis of isoprenoids in Mycobacterium tuberculosis has been reported as an interesting pathway to target. In this context, 2C-methyl-D-erythritol 4-phosphate (MEP) pathway of M. tuberculosis has drawn attention. The MEP pathway begins with the condensation of glyceraldehyde 3-phosphate and pyruvate forming 1-deoxy-D-xylulose 5-phosphate (DXP) which is catalyzed by 1-deoxy-D-xylulose 5-phosphate synthase (DXS). As there is no X-ray structure was reported for this target, comparative modeling was used to generate the three dimensional structure. The structure was further validated by PROCHECK, VERIFY-3D, PROSA, ERRAT and WHATIF. Molecular docking studies was performed with the substrate (Thiamine pyrophosphate) and the reported inhibitor 2-methyl-3-(4-fluorophenyl)-5-(4-methoxy-phenyl)-4H-pyrazolol[1,5-a]pyrimidin-7-one) against the developed model to identify the crucial residues in the active site. This study may further be useful to provide structure based drug design.

• BMB Reports
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• 제45권12호
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• pp.736-741
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• 2012

Certain members of the cytochromes P450 superfamily metabolize polyunsaturated long-chain fatty acids to several classes of oxygenated metabolites. An approach based on in silico analysis predicted that Streptomyces peucetius CYP107N3 might be a fatty acid-metabolizing enzyme, showing high homology with epoxidase enzymes. Homology modeling and docking studies of CYP107N3 showed that oleic acid can fit directly into the active site pocket of the double bond of oleic acid within optimum distance of $4.6{\AA}$ from the Fe. In order to confirm the epoxidation activity proposed by in silico analysis, a gene coding CYP107N3 was expressed in Escherichia coli. The purified CYP107N3 was shown to catalyze $C_9-C_{10}$ epoxidation of oleic acid in vitro to 9,10-epoxy stearic acid confirmed by ESI-MS, HPLC-MS and GC-MS spectral analysis.

• Bulletin of the Korean Chemical Society
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• 제30권11호
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• pp.2523-2531
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• 2009

Effects of some diacid, diamine and dinitro aromatic compounds on the structure and activity of adenosine deaminase (ADA) were investigated by UV-Vis spectrophotometry in 50 mM phosphate buffer at pH = 7.5 and 27 ${^{\circ}C}$ and molecular docking studies. The results showed that all tested ligands are showing inhibition; five ligands are uncompetitive and other two ligands are mixed of competitive and noncompetetive inhibitors with majority of competitive behavior. For the later case analysis was done based on competitive inhibition. Diacids have larger size and higher inhibition constant ($K_I$) relative to others. A logical correlation between calculated free energy of binding and experimental values was obtained for un-competitive. Experimental and calculated data showed that competitive inhibitors are distributed near the active site of enzyme and form several cluster of ranks, whereas uncompetitive inhibitors bind to the enzyme-substrate complex and distributed far from the active site. Results of structure-activity relationship showed that, larger, more hydrophobe, less spherical and more aromatic ligands have higher inhibition constants.

• Bulletin of the Korean Chemical Society
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• 제31권3호
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• pp.606-610
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• 2010

Aminoacyl-tRNA synthetases (aaRSs) play vital roles in protein biosynthesis of living organisms and are interesting antibacterial drug targets. In order to find out new inhibitor candidate molecules as antibacterial agent, the binding modes of the candidate molecules were investigated at the active sites of aaRSs by molecular docking study. The docking simulations were performed with 48 compounds from four different scaffolds into the eight different aaRSs. The results show that scaffolds 3 and 4 compounds have consistently better binding capabilities, specifically for HisRS (E. coli) and IleRS (S. aureus). The binding modes of the best compounds with the proteins were well compatible with those of two ligands in crystal structures. Therefore, we expect that the final compounds we present may have reasonable aaRS inhibitory activity.