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

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.9
• /
• pp.3817-3825
• /
• 2015

Background: The human protein methyl-transferase DOT1L catalyzes the methylation of histone H3 on lysine 79 (H3K79) at homeobox genes and is also involved in a number of significant processes ranging from gene expression to DNA-damage response and cell cycle progression. Inhibition of DOT1L activity by shRNA or small-molecule inhibitors has been established to prevent proliferation of various MLL-rearranged leukemia cells in vitro, establishing DOT1L an attractive therapeutic target for mixed lineage leukemia (MLL). Most of the drugs currently in use for the MLL treatment are reported to have low efficacy, hence this study focused on various natural compounds which exhibit minimal toxic effects and high efficacy for the target receptor. Materials and Methods: Structures of human protein methyl-transferase DOT1L and natural compound databases were downloaded from various sources. Virtual screening, molecular docking, dynamics simulation and drug likeness studies were performed for those natural compounds to evaluate and analyze their anti-cancer activity. Results: The top five screened compounds possessing good binding affinity were identified as potential high affinity inhibitors against DOT1L's active site. The top ranking molecule amongst the screened ligands had a Glide g-score of -10.940 kcal/mol and Glide e-model score of -86.011 with 5 hydrogen bonds and 12 hydrophobic contacts. This ligand's behaviour also showed consistency during the simulation of protein-ligand complex for 20000 ps, which is indicative of its stability in the receptor pocket. Conclusions: The ligand obtained out of this screening study can be considered as a potential inhibitor for DOT1L and further can be treated as a lead for the drug designing pipeline.

• Genomics & Informatics
• /
• v.19 no.1
• /
• pp.6.1-6.10
• /
• 2021

Vascular endothelial growth factor (VEGF) is expressed at elevated levels by most cancer cells, which can stimulate vascular endothelial cell growth, survival, proliferation as well as trigger angiogenesis modulated by VEGF and VEGFR (a tyrosine kinase receptor) signaling. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2. Targeting this signaling molecule and its receptor is a novel approach for blocking angiogenesis. In recent years virtual high throughput screening has emerged as a widely accepted powerful technique in the identification of novel and diverse leads. The high resolution X-ray structure of VEGF has paved the way to introduce new small molecular inhibitors by structure-based virtual screening. In this study using different alkaloid molecules as potential novel inhibitors of VEGF, we proposed three alkaloid candidates for inhibiting VEGF and VEGFR mediated angiogenesis. As these three alkaloid compounds exhibited high scoring functions, which also highlights their high binding ability, it is evident that these alkaloids can be taken to further drug development pipelines for use as novel lead compounds to design new and effective drugs against cancer.

• The Journal of Korean Institute of Communications and Information Sciences
• /
• v.27 no.4C
• /
• pp.308-315
• /
• 2002

Guaranteed frame rate (GFR) service has been defied to provide minimum cell rate (MCR) guarantees for virtual connections (VCs) carrying Internet traffic in ATM networks and allow them to fairly share residual bandwidth. The simplest switch implementation mechanism to support the GFR service in ATM networks consists of the frame-based generic cell rate algorithm (F-GCRA) frame classifier and the early packet discard (EPD)-like buffer acceptance algorithm in a single FIFO buffer. This mechanism is simple, but has foiled to guarantee the same bandwidth as an MCR to a VC that has reserved a relatively large MCR. This paper applies the packet spacing scheme to TCP traffic to alleviate its burstness, so as to guarantee a larger MCR to a VC. In addition, the random early detection (RED) scheme is added to the buffer acceptance algorithm in order to improve fairness in use of residual bandwidth. Simulation results show that the applied two schemes improve a quality of service (QoS) in the GFR service for the TCP traffic.

• Journal of the Korea Academia-Industrial cooperation Society
• /
• v.12 no.7
• /
• pp.2939-2944
• /
• 2011

The performance and efficiency of a Molten Carbonate Fuel Cell system will improve with the aids of numerical simulations such as finite element analysis. For best simulation results, the virtual model must accurately reflect the actual model including the material properties. It is very difficult, however, to make a detailed numerical model of the stack that consists of hundreds of layers of unit cells composed of various materials like metal, ceramics, polymer, etc. Instead, a practical approach is to find a homogenized material property of the stack as a whole as an approximate replacement. In this paper, the compression ratio of a unit cell is introduced, and a new method is proposed to estimate the homogeneous material properties for both the active and the manifold regions of the stack under the assumption that the compressive deformation occurs only at the separators and matrices in the unit cells. The estimated properties are applied successfully to simulating an actual stack.

• Journal of Integrative Natural Science
• /
• v.16 no.3
• /
• pp.81-95
• /
• 2023

Colorectal cancer is one of the most common types of cancer worldwide, ranking third after lung and breast cancer in terms of global prevalence. With an expected 1.93 million new cases and 935,000 deaths in 2020, it is more prevalent in males than in women. Evidence has shown that during the later stages of colon cancer, STAT1 promotes tumor progression by promoting cell survival and resistance to chemotherapy. Recent studies have shown that inhibiting STAT1 pathway leads to a reduction in tumor cell proliferation and growth, and can also promote apoptosis in colon cancer cells. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened FDA database against STAT1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top 10 compounds to be more specific with STAT1 comparing the affinity with STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. The drugs that showed higher affinity were subjected to Conceptual - Density functional theory. Besides, the Molecular dynamic simulation was also carried out for the selected leads. We also validated in-vitro against colon cancer cell lines. The results showed mainly Acetyldigitoxin has shown better binding to the target. From this study, we can predict that the drug Acetyldigitoxin has shown noticeable inhibitory efficiency against STAT1, which in turn can also lead to the reduction of tumor cell growth in colon cancer.

• The Journal of Korean Institute of Communications and Information Sciences
• /
• v.19 no.10
• /
• pp.1935-1944
• /
• 1994

FMS is a distributed system composed of various programmable manufacturing hardware such as robots and NC machines. For the autonomous operation of such a system, an integrated software layer for the control and monitoring in needed on top of the manufacturing hardware. However, constructing and maintaining such a software layer is difficult due to the complexity of a underlying FMS and its frequently changing nature. To cope with this problem, this paper proposes an object-oriented FMS integration model, in which objects acting as virtual manufacturing cells are instantiated for each physical cell in the underlying object-oriented database. Various other entities involved in manufacturing processes and their relationship to the cell objects are also captured in the database. This paper describes the structure of this object-oriented FMS database on our prototype implementation called FREE.

• Proceedings of the Korean Society of Precision Engineering Conference
• /
• 1997.10a
• /
• pp.519-522
• /
• 1997

In this study, the collision free path planning method of the articulated manipulator using sequential search is proposed. This method is to find the joint path of the manipulator with many degrees of freedom from the distal joint to the proximal one. To do this, the initial work space of the gantry manipulator, which is a remote maintenance equipment of the radioactive environment, is defined from the condition that the distal joint configuration is determined by the posture of maintenance. Then, 2-dimensional configuration space with the obstacle area is represented and the collision free path of manipulator is searched in the configuration space. And, this method is verified using the graphic simulation in virtual workcell for the spent fuel disassembling processes. The result of this study can be effectively used in implementing the maintenance processes for the hot cell equipment and enhance the reliability of the spent fuel management.

• Journal of KIISE:Information Networking
• /
• v.28 no.3
• /
• pp.417-425
• /
• 2001

Since First-Come-First-Served discipline makes it difficult to satisfy the diverse quality of scrvicc(QoS) requirements for each c-oonection, traffic isolation has been proposed for guaranteeing the desired QoS through explicit bandwidth allocation to each virtual connection(VC) in A TM networks. For this purpose, we propose a rate-controlled cell multiplexer using a simple "periodic token-based regulator" per- Vc. The proposed multiplexer realizes VC isolation, while still operating work'||'&'||'not;conservingly. We first discuss its major properties, and then examine its features with respect to the characteristics of the output traffic streams and the traffic isolation of individual VC's, by simulation.n.

• Journal of the Korea Computer Graphics Society
• /
• v.6 no.4
• /
• pp.9-14
• /
• 2000

Non-Photorealistic rendering techniques, such as toon rendering, can enhance the quality of hand-drawn cell-animation images greatly with less effort. For this reason, to on rendering is one of the popular techniques used in the cell-animation image production field. The existing toon rendering techniques, however, have not been effective enough for the real-time image processing that the techniques have not been adequate for some processes that needs immediate responses such as virtual-realities, or video games. This paper will suggest the real-time toon rendering to overcome the limits through real-time outline detection and phong shading. In addition, a effective result-image is created as adding a shadow and a execution time remains by real-time through fast shadow generation algorithm.