• 한국정보과학회:학술대회논문집
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• 한국정보과학회 2004년도 봄 학술발표논문집 Vol.31 No.1 (A)
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• pp.466-468
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• 2004

Molecular modelling은 시뮬레이션을 통해 온도, 압력 등과 같은 분자 운동에 영향을 미칠 수 있는 요소를 설정한 후 분자의 움직임을 관찰하는 방법으로 신약, 신소재, 고분자 개발에 있어서 연구 개발 기간을 단축하는 효과적인 방법이다. 기존의 molecular modelling 어플리케이션들은 슈퍼컴퓨터나 단일 클러스터를 이용하여 작업을 수행하도록 설계되어 비용과 성능 측면에서 문제점을 가지고 있다. 1590년대 중반 지리적으로 분산되어 있는 광범위한 자원들을 공유하여 장기간 소요되는 컴퓨팅 작업의 성능 향상 및 비용절감을 목적으로 하는 그리드(grid)가 등장하였다. 이에 본 연구에서는 효율적이면서도 저비용을 갖는 molecular modelling 어플리케이션 개발을 위해 그리드를 기반으로 최적 자원 선택 브로커를 이용하는 molecular docking 어플리케이션을 제안한다. 이를 위해 우리는 molecular docking을 수행하는 그리드 환경의 계층 구조를 설계하고 효율적 작업 수행을 위한 최적 자원 선택 브로커를 설계하였다. 그리고 그리드 환경에서 molecular docking 어플리케이션의 효과적인 수행을 위해 molecular docking 연산 모델을 정의하고 필요한 molecular docking 어플리케이션의 요소들을 설계하였다.

• Bulletin of the Korean Chemical Society
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• 제24권9호
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• pp.1256-1260
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• 2003

Two O-methyltransferases, OMTII-1 and OMTII-4 of meadow rue Thalictrum tuberosum showed a high sequence identity. Of 364 amino acids only one residue is not the same, which is Tyr21 or Cys21. Even if the 21st residues in these OMTs are not included in the binding sites of the enzymes, binding affinities of the enzyme homodimers over the same substrate are very different. While the binding affinity of one homodimer over caffeic acid is 100%, that of the other is 25%. Authors tried to predict the three-dimensional structures of Thalictrum tuberosum O-methyltransferases using homology-based modelling by a comparison with caffeic acid O-methyltransferase, and explain the reason of the phenomenon mentioned above based on their three dimensional structural studies. In the enzyme homodimer, the better binding affinity may be caused by the shorter distance between the 21st residue and the binding site of the other monomer.

• The Plant Pathology Journal
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• 제33권6호
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• pp.529-542
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• 2017

Control of plant diseases is largely dependent on use of agrochemicals. However, there are widening gaps between our knowledge on plant diseases gained from genetic/mechanistic studies and rapid translation of the knowledge into target-oriented development of effective agrochemicals. Here we propose that the time is ripe for computer-aided drug discovery/design (CADD) in molecular plant pathology. CADD has played a pivotal role in development of medically important molecules over the last three decades. Now, explosive increase in information on genome sequences and three dimensional structures of biological molecules, in combination with advances in computational and informational technologies, opens up exciting possibilities for application of CADD in discovery and development of agrochemicals. In this review, we outline two categories of the drug discovery strategies: structure- and ligand-based CADD, and relevant computational approaches that are being employed in modern drug discovery. In order to help readers to dive into CADD, we explain concepts of homology modelling, molecular docking, virtual screening, and de novo ligand design in structure-based CADD, and pharmacophore modelling, ligand-based virtual screening, quantitative structure activity relationship modelling and de novo ligand design for ligand-based CADD. We also provide the important resources available to carry out CADD. Finally, we present a case study showing how CADD approach can be implemented in reality for identification of potent chemical compounds against the important plant pathogens, Pseudomonas syringae and Colletotrichum gloeosporioides.

• Bulletin of the Korean Chemical Society
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• 제23권1호
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• pp.9-10
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• 2002

• Biomolecules & Therapeutics
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• 제29권5호
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• pp.506-518
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• 2021

The imprinted tumour suppressor NOEY2 is downregulated in various cancer types, including ovarian cancers. Recent data suggest that NOEY2 plays an essential role in regulating the cell cycle, angiogenesis and autophagy in tumorigenesis. However, its detailed molecular function and mechanisms in ovarian tumours remain unclear. In this report, we initially demonstrated the inhibitory effect of NOEY2 on tumour growth by utilising a xenograft tumour model. NOEY2 attenuated the cell growth approximately fourfold and significantly reduced tumour vascularity. NOEY2 inhibited the phosphorylation of the signalling components downstream of phosphatidylinositol-3'-kinase (PI3K), including phosphoinositide-dependent protein kinase 1 (PDK-1), tuberous sclerosis complex 2 (TSC-2) and p70 ribosomal protein S6 kinase (p70S6K), during ovarian tumour progression via direct binding to vascular endothelial growth factor receptor-2 (VEGFR-2). Particularly, the N-terminal domain of NOEY2 (NOEY2-N) had a potent anti-angiogenic activity and dramatically downregulated VEGF and hypoxia-inducible factor-1α (HIF-1α), key regulators of angiogenesis. Since no X-ray or nuclear magnetic resonance structures is available for NOEY2, we constructed the three-dimensional structure of this protein via molecular modelling methods, such as homology modelling and molecular dynamic simulations. Thereby, Lys15 and Arg16 appeared as key residues in the N-terminal domain. We also found that NOEY2-N acts as a potent inhibitor of tumorigenesis and angiogenesis. These findings provide convincing evidence that NOEY2-N regulates endothelial cell function and angiogenesis by interrupting the VEGFR-2/PDK-1/GSK-3β signal transduction and thus strongly suggest that NOEY2-N might serve as a novel anti-tumour and anti-angiogenic agent against many diseases, including ovarian cancer.

• 통합자연과학논문집
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• 제11권2호
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• pp.121-129
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• 2018

CXCR6 is a major target in drug design as it is a determinant receptor in many diseases like AIDS, Type I Diabetes, some cancer types, atherosclerosis, tumor formation, liver disease and steatohepatitis. In this study, we propose the active site residues of CXCR6 molecule. We employed homology modelling and molecular docking approach to generate the 3D structure for CXCR6 and to explore its interaction between the antagonists and agonists. 3D models were generated using 14 different templates having high sequence identity with CXCR6. Surflex docking studies using pyridine and pyrimidine derivatives enabled the analysis of the binding site and finding of the important residues involved in binding. 3D structure of CXCL16, a natural ligand for CXCR6, was modelled using PHYRE and protein - protein docking was performed using ClusPro. The residues which were found to be crucial in interaction with the ligand are THR110, PHE113, TYR114, GLN160, GLN195, CYS251 and SER255. This study can be used as a guide for therapeutic studies of human CXCR6.

• Bulletin of the Korean Chemical Society
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• 제28권2호
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• pp.200-206
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• 2007

Pharmacophore models for lymphocyte-specific protein tyrosine kinase (P56 LCK) were developed using CATALYST HypoGen with a training set comprising of 25 different P56 LCK inhibitors. The best quantitative pharmacophore hypothesis comprises of one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic aliphatic and one ring aromatic features with correlation coefficient of 0.941, root mean square deviation (RMSD) of 0.933 and cost difference (null cost-total cost) of 66.23. The pharmacophore model was validated by two methods and the validated model was further used to search databases for new compounds with good estimated LCK inhibitory activity. These compounds were evaluated for their binding properties at the active site by molecular docking studies using GOLD software. The compounds with good estimated activity and docking scores were evaluated for physiological properties based on Lipinski's rules. Finally 68 compounds satisfied all the properties required to be a successful inhibitor candidate.

• Biotechnology and Bioprocess Engineering:BBE
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• 제11권3호
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• pp.223-229
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• 2006

In this study, we have conducted kinetics and modelling studies of Centella asiatica cell growth and substrate uptake, in an attempt to evaluate cell growth for a better understanding and control of the process. In our bioreactor cultivation experiment, we observed a growth rate of 0.18/day, a value only 20% higher than was seen in the shake flask cultivation trial. However, the observed maximum cell dry weight in the shake flask, 10.5g/L, was 14% higher than was achieved in the bioreactor. Ninety seven percentage confidence was achieved via the fitting of three unstructured growth models; the Monod, Logistic, and Gompertz equations, to the cell growth data. The Monod equation adequately described cell growth in both cultures. The specific growth rate, however, was not effectively predicted with the Logistic and Gompertz equations, which resulted in deviations of up to 73 and 393%, respectively. These deviations in the Logistic and Gompertz models may be attributable to the fact that these models were developed for substrate-independent growth and fungi growth, respectively.

• BMB Reports
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• 제45권4호
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• pp.259-264
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• 2012

Accumulation of modified nucleotides is defective to various cellular processes, especially those involving DNA and RNA. To be viable, organisms possess a number of (deoxy)nucleotide phosphohydrolases, which hydrolyze these nucleotides removing them from the active NTP and dNTP pools. Deamination of purine bases can result in accumulation of such nucleotides as ITP, dITP, XTP and dXTP. E. coli RdgB has been characterised as a deoxyribonucleoside triphosphate pyrophosphohydrolase that can act on these nucleotides. S. cerevisiae homologue encoded by YJR069C was purified and its (d)NTPase activity was assayed using fifteen nucleotide substrates. ITP, dITP, and XTP were identified as major substrates and kinetic parameters measured. Inhibition by ATP, dATP and GTP were established. On the basis of experimental and published data, modelling and simulation of ITP, dITP, XTP and dXTP metabolism was performed. (d)ITP/(d)XTPase is a new example of enzyme with multiple substrate-specificity demonstrating that multispecificity is not a rare phenomenon

• Journal of Microbiology and Biotechnology
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• 제2권2호
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• pp.129-134
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• 1992

Segregational instability of a recombinant plasmid, pDML6, encoding extracellular $\beta$-lactamase in Streptomyces lividans PD6 was characterized by growth kinetic analysis. The quantitative determination of the plasmid harbored in the mycelia was evaluated with mycelia fragmented mechanically, and also with colonies regenerated from protoplasts. Conditions for the formation of protoplasts and regeneration of protoplasts were established. The maximal specific growth rates of the host strain and the plasmid-harboring strain in a chemically defined medium without selection pressure were the same. The probability of plasmid loss from the harbouring cells was higher at higher growth rates. Mathematical models for the prediction of cell growth, substrate uptake, and accumulation of the cloned gene product were developed.