• Translational and Clinical Pharmacology
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• 제26권4호
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• pp.145-149
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• 2018

Cases of drug-induced QT prolongation and sudden cardiac deaths resulted in market withdrawal of many drugs and world-wide regulatory changes through accepting the ICH guidelines E14 and S7B. However, because the guidelines were not comprehensive enough to cover the electrophysiological changes by drug-induced cardiac ion channel blocking, CiPA was initiated by experts in governments and academia in the USA, Europe, and Japan in 2013. Five years have passed since the launch of the CiPA initiative that aimed to improve the current ICH guidelines. This report reviews the current achievements of the CiPA initiative and explores unresolved issues.

• Journal of Industrial and Engineering Chemistry
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• 제67권
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• pp.293-300
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• 2018

Lipocalins are diverse group of small extracellular proteins found in various organisms. In this study, members of 10 non-homologous lipocalin-ligand crystal complex structures were remodeled using rigid and flexible ligand modes to validate the prediction efficiency of molecular docking simulation. The modeled ligand conformations indicated a high prediction accuracy in rigid ligand mode using cluster based analysis for most cases whereas the flexible ligand mode required further considerations such as ligand binding energy and RMSD for some cases. This in silico study is expected to serve as a platform in the screening of novel ligands against lipocalin family of proteins.

• Journal of Microbiology and Biotechnology
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• 제17권8호
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• pp.1236-1241
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• 2007

Five fusion proteins between Z domains derived from Staphylococcal Protein A and Green Fluorescent Protein or Human Proinsulin were produced on the periplasm of Escherichia coli. The effects of the molecular weight and amino acid composition of the translocated peptide, culture medium composition, and growth phase of the bacterial culture were analyzed regarding the expression and periplasmic secretion of the recombinant proteins. It was found that secretion was not affected by the size of the translocated peptide (17-42 kDa) and that the highest periplasmic production values were obtained on the exponential phase of growth. Moreover, the highest periplasmic values were obtained in minimal medium, showing the relevance of the culture medium composition on secretion. In silico prediction analysis suggested that with respect to the five proteins used in this study, those that are prone to form ${\alpha}$-helix structures are more translocated to the periplasm.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.192.2-193
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• 2003

Capsaicin, a pungent ingredient in chili pepper, is known to excite sensory neurons that mediate pain sensation. This effect of capsaicin is determined by unique receptors and the capsaicin receptor (transient receptor potential subfamily V, member 1 (TRPV1)) was cloned recently. TRPV1 contains six transmembrane domains and three ankyrin repeats at N-terminal. This characteristic architecture is common in other ion channel in TRPV families. (omitted)

• Journal of Microbiology and Biotechnology
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• 제22권1호
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• pp.46-49
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• 2012

The Vibrio vulnificus vuuA gene, of which expression is repressed by a complex of iron and ferric uptake regulator (Fur), was characterized to localize the Fur-binding site in its upstream regulatory region. In silico analysis suggested the presence of two possible Fur-binding sites; one is a classical Fur-box and the other is a previously reported distinct Fur-binding site. Site-directed mutagenesis and DNase I protection assays revealed the binding site for the iron-Fur complex, which includes an extended inverted repeat containing a homologous sequence to the classical Fur-box.

• Genomics & Informatics
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• 제12권4호
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• pp.171-180
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• 2014

Aberrant DNA methylation, as an epigenetic marker of cancer, influences tumor development and progression. We downloaded publicly available DNA methylation and gene expression datasets of matched cancer and normal pairs from the Cancer Genome Atlas Data Portal and performed a systematic computational analysis. This study has three aims to screen genes that show hypermethylation and downregulated patterns in colorectal cancers, to identify differentially methylated regions in one of these genes, SFRP1, and to test whether the SFRP genes affect survival or not. Our results show that 31 hypermethylated genes had a negative correlation with gene expression. Among them, SFRP1 had a differentially methylated pattern at each methylation site. We also show that SFRP1 may be a potential biomarker for colorectal cancer survival.

• 통합자연과학논문집
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• 제15권4호
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• pp.171-177
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• 2022

ROS1 (c-ros oncogene) is one of the gene with mutation in NSCLC (non-small cell lung cancer). The increased expression of ROS1 is leading to the increase proliferation of cell, cell migration and survival. Crizotinib and Entrectinib are the drugs that have been approved by FDA against ROS1 protein, but recently patients started to develop resistance against Crizotinib and there is a need of new drug that could act as an effective drug against ROS1 for NSCLC. In this study, we have performed virtual screening, where compounds are taken from Zinc 15 dataset and molecular docking was performed. The top compounds were taken based upon their binding affinity and their interactions with the residues. The compounds stability and chemical reactivity was also studied through Density Functional theory and their properties. Further study of these compounds could reveal the required information of ROS1-inhibitor complex and in the discovery of potent inhibitors.

• 한국미생물·생명공학회지
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• 제51권1호
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• pp.128-131
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• 2023

Here we report the draft genome sequence of Weissella koreensis strain HJ and genomic analysis of its key features. The genome consists of 1,427,571 bp with a GC content of 35.5%, and comprises 1,376 coding genes. In silico analysis revealed the absence of pathogenic factors within the genome. The genome harbors several genes that play an important role in the survival of the gastrointestinal tract. In addition, a type III polyketide synthase cluster was identified. Pangenome analysis identified 68 unique genes in W. koreensis strain HJ. The genome information of this strain provides the basis for understanding its probiotic properties.

• Genomics & Informatics
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• 제21권3호
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• pp.43.1-43.13
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• 2023

Melanin is synthesized by tyrosinase to protect the skin from ultraviolet light. However, overproduction and accumulation of melanin can result in hyperpigmentation and skin melanoma. Tyrosinase inhibitors are commonly used in the treatment of hyperpigmentation. Natural tyrosinase inhibitors are often favoured over synthetic ones due to the potential side effects of the latter, which can include skin irritation, allergies, and other adverse reactions. Nuciferine, an alkaloid derived from Nelumbo nucifera, exhibits potent antioxidant and anti-proliferative properties. This study focused on the in silico screening of nuciferine for anti-tyrosinase activity, using kojic acid, ascorbic acid, and resorcinol as standards. The tyrosinase protein target was selected through homology modeling. The residues of the substrate binding pocket and active site pockets were identified for the purposes of grid box optimization and docking. Therefore, nuciferine is a potent natural tyrosinase inhibitor and shows promising potential for application in the treatment of hyperpigmentation and skin melanoma.

• Molecules and Cells
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• 제25권3호
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• pp.397-406
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• 2008

Computational modeling of signal transduction is currently attracting much attention as it can promote the understanding of complex signal transduction mechanisms. Although several mathematical models have been used to examine signaling pathways, little attention has been given to crosstalk mechanisms. In this study, an attempt was made to develop a computational model for the pathways involving growth-factor-mediated mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3'-kinase/protein kinase B (PI3K/Akt). In addition, the dynamics of the protein activities were analyzed based on a set of kinetic data. The simulation approach integrates the information on several levels and predicts systems behavior. The in-silico analysis conducted revealed that the Raf and Akt pathways act independently.