• Proceedings of the Korean Society for Bioinformatics Conference
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• 2005.09a
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• pp.249-255
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• 2005

Angiotensin-converting enzyme (ACE) is primarily responsible for human hypertension. Current ACE drugs show serious cough and angiodema health problems due to the un-specific activity of the drug to ACE protein. The availability of ACE crystal structure (1UZF) provided the plausible biological orientation of inhibitors to ACE active site (C-domain). Three-dimensional quantitative structure-activity relationship (3D-QSAR) models have been constructed using the comparative molecula. field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for a series of 28 ACE inhibitors. Alignment for CoMFA obtained by docking ligands to 1UZF protein using FlexX program showed better statistical model as compared to superposition of corresponding atoms. The statistical parameters indicate reasonable models for both CoMFA (q$^2$ = 0.530, r$^2$ = 0.998) and CoMSIA (q$^2$= 0.518, r$^2$ = 0.990). The 3D-QSAR analyses provide valuable information for the design of ACE inhibitors with potent activity towards C-domain of ACE. The group substitutions involving the phenyl ring and carbon chain at the propionyl and sulfonyl moieties of captopril are essential for specific activity to ACE.

• Proceedings of the KOSOMBE Conference
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• v.1997 no.05
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• pp.72-74
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• 1997

We have developed a 3-D image processing and display technique that include image resampling, modification of MIP, and fusion of MIP image and volumetric rendered image. This technique facilitates the visualization of the three-dimensional spatial relationship between vasculature and surrounding organs by overlapping the MIP image on the volumetric rendered image of the organ. We applied this technique to a MR brain image data to produce an MRI angiogram that is overlapped with 3-D volume rendered image of brain. MIP technique was used to visualize the vasculature of brain, and volume rendering was used to visualize the other structures of brain. The two images are fused after adjustment of contrast and brightness levels of each image in such a way that both the vasculature and brain structure are well visualized either by selecting the maximum value of each image or by assigning different color table to each image. The resultant image with this technique visualizes both the brain structure and vasculature simultaneously, allowing the physicians to inspect their relationship more easily. The presented technique will be useful for surgical planning for neurosurgery.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.6
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• pp.517-523
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• 2013

Naphthyridine compounds are important, because they exhibit various biological activities including anticancer, antimicrobial, and anti-inflammatory activity. Some naphthyridines have antimitotic effects or demonstrate anticancer activity by inhibiting topoisomerase II. These compounds have been investigated as potential anticancer agents, and several compounds are now part of clinical trials. A series of naphthyridine derivatives were evaluated for their in vitro cytotoxic activities against human cervical cancer (HeLa), leukemia (HL-60), and prostate cancer (PC-3) cell lines using an MTT assay. Some compounds (14, 15, and 16) were more potent than colchicine against all three human cancer cell lines and compound (16) demonstrated potency with $IC_{50}$ values of 0.7, 0.1, and $5.1{\mu}M$, respectively. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used for quantitative structure-activity relationship (QSAR) molecular modeling of these compounds. We obtained accurate and predictive three-dimensional QSAR (3D-QSAR) models as indicated by the high PLS parameters of the HeLa ($q^2$, 0.857; $r^2$, 0.984; $r^2\;_{pred}$, 0.966), HL-60 ($q^2$, 0.777; $q^2$, 0.937; $r^2\;_{pred}$, 0.913), and PC-3 ($q^2$, 0.702; $q^2$, 0.983; $r^2\;_{pred}$, 0.974) cell lines. The 3D-QSAR contour maps suggested that the C-1 NH and C-4 carbonyl group of the naphthyridine ring and the C-2 naphthyl ring were important for cytotoxicity in all three human cancer cell lines.

• Applied Biological Chemistry
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• v.48 no.3
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• pp.252-257
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• 2005

Three-dimensional quantitative structure-activity relationships (3D-QSARs) for the herbicidal activities against pre-emergence barnyard grass (Echinochloa crus-galli) by new 2-(4-(6-chloro-2-benzoxazolyloxy)phenoxy)-N-phenylpropion amide derivatives were studied quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methodologies. The best CoMFA model (AI-2) and CoMSIA model (AII-4) were derived from an atom based fit alignment and a combination of CoMFA fields. The herbicidal activities from CoMFA and CoMSIA contour maps showed that the activity will be able to be increased according to the substituents variation on the N-phenyl ring.

• Archives of Pharmacal Research
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• v.29 no.1
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• pp.50-58
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• 2006

Translationally controlled tumor protein (TCTP), also known as histamine releasing factor (HRF), is found abundantly in different eukaryotic cell types. The sequence homology of TCTP between different species is very high, belonging to the MSS4/DSS4 superfamily of proteins. TCTP is involved in both cell growth and human late allergy reaction, as well as having a calcium binding property; however, its primary biological functions remain to be clearly elucidated. In regard to many possible functions, the TCTP of Plasmodium falciparum (Pf) is known to bind with an antimalarial agent, artemisinin, which is activated by heme. It is assumed that the endoperoxide-bridge of artemisinin is opened up by heme to form a free radical, which then eventually alkylates, probably to the Cys14 of PfTCTP. Study of the docking of artemisinin with heme, and subsequently with PfTCTP, was carried out to verify the above hypothesis on the basis of structural interactions. The three dimensional (3D) structure of PfTCTP was built by homology modeling, using the NMR structure of the TCTP of Schizosaccharomyces pombe as a template. The quality of the model was examined based on its secondary structure and biological function, as well as with the use of structure evaluating programs. The interactions between artemisinin, heme and PfTCTP were then studied using the docking program, FlexiDock. The center of the peroxide bond of artemisinin and the Fe of heme were docked within a short distance of $2.6{\AA}$, implying the strong possibility of an interaction between the two molecules, as proposed. When the activated form of artemisinin was docked on the PfTCTP, the C4-radical of the drug faced towards the sulfur of Cys14 within a distance of $2.48{\AA}$, again suggesting the possibility of alkylation having occurred. These results confirm the proposed mechanism of the antimalarial effect of artemisinin, which will provide a reliable method for establishing the mechanism of its biological activity using a molecular modeling study.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.3
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• pp.237-243
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• 2013

B13 is a ceramide analogue and apoptosis inducer with potent cytotoxic activity. A series of arylpropyl sulfonamide analogues of B13 were evaluated for their cytotoxicity using MTT assays in prostate cancer PC-3 and leukemia HL-60 cell lines. Some compounds (4, 9, 13, 14, 15, and 20) showed stronger activities than B13 in both tumor cell lines, and compound (15) gave the most potent activity with $IC_{50}$ values of 29.2 and 20.7 ${\mu}M$, for PC-3and HL-60 cells, respectively. Three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed to build highly reliable and predictive CoMSIA models with cross-validated $q^2$ values of 0.816 and 0.702, respectively. Our results suggest that long alkyl chains and a 1R, 2R configuration of the propyl group are important for the cytotoxic activities of arylpropyl sulfonamides. Moreover, the introduction of small hydrophobic groups in the phenyl ring and sulfonamide group could increase biological activity.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2005.09a
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• pp.139-143
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• 2005

Cytochrome P450 14${\alpha}$-sterol demethylase enzyme (CYP51) is the target a of azole type antifungals. The azole blocks the ergosterol synthesis and thereby inhibits fungal growth. A three-dimensional (3D) homology model of CYP51 from Candida albicans was constructed based on the X-ray crystal structure of CYP51 from Mycobacterium tuberculosis. Using this model, the binding modes for the substrate (24-methylene-24, 25-dihydrolanosterol) and the known inhibitors (fluconazole, voriconazole, oxiconazole, miconazole) were predicted from docking. Virtual screening was performed employing Structure Based Focusing (SBF). In this procedure, the pharmacophore models for database search were generated from the protein-ligands interactions each other. The initial structure-based virtual screening selected 15 compounds from a commercial available 3D database of approximately 50,000 molecule library, Being evaluated by a cell-based assay, 5 compounds were further identified as the potent inhibitors of Candida albicans CYP51 (CACYP51) with low minimal inhibitory concentration (MIC) range. BMD-09-01${\sim}$BMD-09-04 MIC range was 0.5 ${\mu}$g/ml and BMD-09-05 was 1 ${\mu}$g/ml. These new inhibitors provide a basis for some non-azole antifungal rational design of new, and more efficacious antifungal agents.

• Proceedings of the KOSOMBE Conference
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• v.1998 no.11
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• pp.57-59
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• 1998

For medical students and doctors, knowledge of the three-dimensional (3D) structure of brain is very important in diagnosis and treatment of brain diseases. Two-dimensional (2D) tools (ex: anatomy book) or traditional 3D tools (ex: plastic model) are not sufficient to understand the complex structures of the brain. However, it is not always guaranteed to dissect the brain of cadaver when it is necessary. To overcome this problem, the virtual dissection programs of the brain have been developed. However, most programs include only 2D images that do not permit free dissection and free rotation. Many programs are made of radiographs that are not as realistic as sectioned cadaver because radiographs do not reveal true color and have limited resolution. It is also necessary to make the virtual dissection programs of each race and ethnic group. We attempted to make a virtual dissection program using a 3D image of the brain from a Korean cadaver. The purpose of this study is to present an educational tool for those interested in the anatomy of the brain. The procedures to make this program were as follows. A brain extracted from a 58-years old male Korean cadaver was embedded with gelatin solution, and serially sectioned into 1.4 mm-thickness using a meat slicer. 130 sectioned specimens were inputted to the computer using a scanner ($420\times456$ resolution, true color), and the 2D images were aligned on the alignment program composed using IDL language. Outlines of the brain components (cerebrum, cerebellum, brain stem, lentiform nucleus, caudate nucleus, thalamus, optic nerve, fornix, cerebral artery, and ventricle) were manually drawn from the 2D images on the CorelDRAW program. Multimedia data, including text and voice comments, were inputted to help the user to learn about the brain components. 3D images of the brain were reconstructed through the volume-based rendering of the 2D images. Using the 3D image of the brain as the main feature, virtual dissection program was composed using IDL language. Various dissection functions, such as dissecting 3D image of the brain at free angle to show its plane, presenting multimedia data of brain components, and rotating 3D image of the whole brain or selected brain components at free angle were established. This virtual dissection program is expected to become more advanced, and to be used widely through Internet or CD-title as an educational tool for medical students and doctors.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2005.09a
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• pp.173-182
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• 2005

A three dimensional (3D) model for the catalytic region of Type II Pseudomonas sp. USM 4-55 PHA synthase 1 (PhaC1$_{P.sp\;USM\;4-55}$) from residue 267 to residue 484 was developed. Sequence analysis demonstrated that PhaC1$_{P.sp\;USM\;4-55}$ lacked homology with all known structural databases. PSI-BLAST and HMM Superfamily analyses demonstrated that this enzyme belongs to the ${\alpha}/{\beta}$ hydrolase fold family. Threading approach revealed that the most suitable template to use was the Human gastric lipase (1HLG). The superimposition of the predicted PhaC1$_{P.sp\;USM\;4-55}$ model with the 1HLG template structure covering 86.2% of the backbone atoms showed an RMSD of 1.15 ${\AA}$ The catalytic residues comprising of Cys296, Asp451, His452 and His479 were found to be conserved and were located adjacent to each other. We proposed that the catalytic mechanism involved the formation of two tetrahedral intermediates.

• Journal of Biomedical Engineering Research
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• v.19 no.4
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• pp.341-350
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• 1998

The accurate measurement of the femoral anteversion is important for the derotational osteotomy. To estimate femoral anteversion, following three major parameters are required; the neck axis, the long axis, and the knee axis. Conventional methods on the basis of 2D images are ambiguous to determine these major axes. As the femur has a complex 3 dimensional structure, the 3 dimensional model should be applied for accurate and reliable measurement of femoral anteversion. In this thesis, we model femur and define three parameters. The neck axis is defined from the femoral head and neck model. The long axis is determined from the cylindrical model of the femoral shaft. The knee axis is also determined from the model of femoral condyles. According to the definition of the femoral anteversion, the femoral anteversion is efficiently estimated from these models. 20 specimens were tested by the conventional 2D imaging method and 3D imaging method witch was developed by authors and the new 3D modeling method. The study provides accurate, fast and human factor free measurement for femoral anteversion.