Siu Kim

Bio: Siu Kim is an academic researcher from Gyeongsang National University. The author has contributed to research in topics: Information extraction & Natural language processing. The author has an hindex of 4, co-authored 5 publications receiving 37 citations.

Binding Mode Analyses and Pharmacophore Model Development for Stilbene Derivatives as a Novel and Competitive Class of α-Glucosidase Inhibitors

Abstract: Stilbene urea derivatives as a novel and competitive class of non-glycosidic α-glucosidase inhibitors are effective for the treatment of type II diabetes and obesity. The main purposes of our molecular modeling study are to explore the most suitable binding poses of stilbene derivatives with analyzing the binding affinity differences and finally to develop a pharmacophore model which would represents critical features responsible for α-glucosidase inhibitory activity. Three-dimensional structure of S. cerevisiae α-glucosidase was built by homology modeling method and the structure was used for the molecular docking study to find out the initial binding mode of compound 12, which is the most highly active one. The initial structure was subjected to molecular dynamics (MD) simulations for protein structure adjustment at compound 12-bound state. Based on the adjusted conformation, the more reasonable binding modes of the stilbene urea derivatives were obtained from molecular docking and MD simulations. The binding mode of the derivatives was validated by correlation analysis between experimental Ki value and interaction energy. Our results revealed that the binding modes of the potent inhibitors were engaged with important hydrogen bond, hydrophobic, and π-interactions. With the validated compound 12-bound structure obtained from combining approach of docking and MD simulation, a proper four featured pharmacophore model was generated. It was also validated by comparison of fit values with the Ki values. Thus, these results will be helpful for understanding the relationship between binding mode and bioactivity and for designing better inhibitors from stilbene derivatives.

Enhancement of the Chaperone Activity of Alkyl Hydroperoxide Reductase C from Pseudomonas aeruginosa PAO1 Resulting from a Point-Specific Mutation Confers Heat Tolerance in Escherichia coli.

Abstract: Alkyl hydroperoxide reductase subunit C from Pseudomonas aeruginosa PAO1 (PaAhpC) is a member of the 2-Cys peroxiredoxin family. Here, we examined the peroxidase and molecular chaperone functions of PaAhpC using a site-directed mutagenesis approach by substitution of Ser and Thr residues with Cys at positions 78 and 105 located between two catalytic cysteines. Substitution of Ser with Cys at position 78 enhanced the chaperone activity of the mutant (S78C-PaAhpC) by approximately 9-fold compared with that of the wild-type protein (WT-PaAhpC). This increased activity may have been associated with the proportionate increase in the high-molecular-weight (HMW) fraction and enhanced hydrophobicity of S78C-PaAhpC. Homology modeling revealed that mutation of Ser(78) to Cys(78) resulted in a more compact decameric structure than that observed in WT-PaAhpC and decreased the atomic distance between the two neighboring sulfur atoms of Cys(78) in the dimer-dimer interface of S78C-PaAhpC, which could be responsible for the enhanced hydrophobic interaction at the dimer-dimer interface. Furthermore, complementation assays showed that S78C-PaAhpC exhibited greatly improved the heat tolerance, resulting in enhanced survival under thermal stress. Thus, addition of Cys at position 78 in PaAhpC modulated the functional shifting of this protein from a peroxidase to a chaperone.

Effect of initial microstructure on hot forging of mg alloys

Abstract: Magnesium alloys still have a lot of technical challenges to be solved for more applications. There have been many research activities to enhance formability of magnesium alloys. One is to design new alloy composition having better formability. Also, low formability of wrought alloys can be improved by optimizing the processing variables. In the present study, effect of process variables such as forging temperature and forging speed were investigated to forgeability of three different magnesium alloys such as AZ31, AZ61 and ZK60. To understand the effect of process variables more specifically, both numerical and experimental works have been carried out on the model which contains both upsetting and extrusion geometries. Forgeability of magnesium alloys was found to depend more on the forging speed rather than temperature. Forged sample showed a significant activity of twinning, which was found to be closely related with flow uniformity.

Identification of Novel Human HDAC8 Inhibitors by Pharmacophore-based Virtual Screening and Density Functional Theory Approaches

Abstract: Seokmin Kim,†,k Yuno Lee,†,k Songmi Kim,†,k Sang Jik Lee,† Phil Kyeong Heo,† Siu Kim,† Yong Jung Kwon,‡ and Keun Woo Lee†,* †Division of Applied Life Science (BK21 Plus), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Research Institute of Natural Science(RINS), Gyeongsang National University (GNU), Jinju 52828, Republic of Korea. *E-mail: kwlee@gnu.ac.kr ‡Department of Chemical Engineering, Kangwon National University, Chunchon 200-701, Republic of Korea Received August 30, 2017, Accepted December 4, 2017, Published online January 17, 2018

An annotated corpus from biomedical articles to construct a drug-food interaction database

Abstract: While drug-food interaction (DFI) may undermine the efficacy and safety of drugs, DFI detection has been difficult because a well-organized database for DFI did not exist. To construct a DFI database and build a natural language processing system extracting DFI from biomedical articles, we formulated the DFI extraction tasks and manually annotated texts that could have contained DFI information. In this article, we introduced a new annotated corpus for extracting DFI, the DFI corpus.The DFI corpus contains 2270 abstracts of biomedical articles accessible through PubMed and 2498 sentences that contain DFI and/or drug-drug information (DDI), a substantial amount of information about drug/food entities, evidence-levels of abstracts and relations between named entities. BERT models pre-trained on the biomedical domain achieved a F1 score 55.0% in extracting DFI key-sentences. To the best of our knowledge, the DFI corpus is the largest public corpus for drug-food interaction.Our corpus is available at https://github.com/ccadd-snu/corpus-for-DFI-extraction.

Inhibitory kinetics and mechanism of kaempferol on α-glucosidase

Abstract: α-Glucosidase is a therapeutic target for diabetes mellitus, and α-glucosidase inhibitors play a vital role in the treatments for the disease. As a kind of potentially safer α-glucosidase inhibitor, flavonoids have attached much attention currently. In this study, kaempferol was found to show a notable inhibition activity on α-glucosidase in a mixed-type manner with IC50 value of (1.16 ± 0.04) × 10(-5) mol L(-1). Analyses of fluorescence, circular dichroism and Fourier transform infrared spectra indicated that kaempferol bound to α-glucosidase with high affinity which was mainly driven by hydrogen bonds and van der Waals forces, and this binding resulted in conformational alteration of α-glucosidase. Further molecular docking study validated the experimental results. It was proposed that kaempferol may interact with some amino acid residues located within the active site of α-glucosidase, occupying the catalytic center of the enzyme to avoid the entrance of p-nitrophenyl-α-D-glucopyranoside and ultimately inhibiting the enzyme activity.

Inhibitory effect of phloretin on α-glucosidase: Kinetics, interaction mechanism and molecular docking.

Abstract: As the aglycone of phloridzin, phloretin belongs to dihydrochalcone with antioxidant, anti-inflammatory and antimicrobial activities. In this study, multispectroscopic techniques and molecular docking analysis were used to investigate the inhibitory activity and mechanisms of phloretin on α-glucosidase. The results showed that phloretin reversibly inhibited α-glucosidase in a mixed-type manner and the value of IC50 was 31.26μgL-1. The intrinsic fluorescence of α-glucosidase was quenched by the interactions with phloretin through a static quenching mechanism and spontaneously formed phloretin-α-glucosidase complex by the driving forces of van der Waals force and hydrogen bond. Atomic force microscope (AFM) studies and FT-IR measurements suggested that the interactions could change the micro-environments and conformation of the enzymes and the molecular docking analysis displayed the exact binding site of phloretin on α-glucosidase. These results indicated that phloretin is a strong α-glucosidase inhibitor, thus could be contribute to the improvement of diabetes mellitus.

Food protein-derived bioactive peptides in management of type 2 diabetes

Abstract: Type 2 diabetes (T2D), one of the major common human health problems, is growing at an alarming rate around the globe. Alpha-glucosidase and dipeptidyl peptidase IV (DPP-IV) enzymes play a significant role in development of T2D. Hence, reduction or inhibition of their activity can be one of the important strategies in management of T2D. Studies in the field of bioactive peptides have shown that dietary proteins could be natural source of alpha-glucosidase and DPP-IV inhibitory peptides. The purpose of this review is to provide an overview of food protein-derived peptides as potential inhibitors of alpha-glucosidase and DPP-IV with major focus on milk proteins. Efforts have been made to review the available information in literature on the relationship between food protein-derived peptides and T2D. This review summarizes the current data on alpha-glucosidase and dipeptidyl peptidase IV inhibitory bioactive peptides derived from proteins and examines the potential value of these peptides in the treatment and prevention of T2D. In addition, the proposed modes of inhibition of peptide inhibitors are also discussed. Studies revealed that milk and other food proteins-derived bioactive peptides play a vital role in controlling T2D through several mechanisms, such as the satiety response, regulation of incretin hormones, insulinemia levels, and reducing the activity of carbohydrate degrading digestive enzymes. The bioactive peptides could be used in prevention and management of T2D through functional foods or nutraceutical supplements. Further clinical trials are necessary to validate the findings of in vitro studies and to confirm the efficiency of these peptides for applications.

Microstructure, texture and mechanical behavior characterization of hot forged cast ZK60 magnesium alloy

Abstract: The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.jmst.2017.04.004 © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

Histone deacetylase 8 (HDAC8) and its inhibitors with selectivity to other isoforms: An overview

Abstract: The histone deacetylases (HDACs) enzymes provided crucial role in transcriptional regulation of cells through deacetylation of nuclear histone proteins. Discoveries related to the HDAC8 enzyme activity signified the importance of HDAC8 isoform in cell proliferation, tumorigenesis, cancer, neuronal disorders, parasitic/viral infections and other epigenetic regulations. The pan-HDAC inhibitors can confront these conditions but have chances to affect epigenetic functions of other HDAC isoforms. Designing of selective HDAC8 inhibitors is a key feature to combat the pathophysiological and diseased conditions involving the HDAC8 activity. This review is concerned about the structural and positional aspects of HDAC8 in the HDAC family. It also covers the contributions of HDAC8 in the pathophysiological conditions, a preliminary discussion about the recent scenario of HDAC8 inhibitors. This review might help to deliver the structural, functional and computational information in order to identify and design potent and selective HDAC8 inhibitors for target specific treatment of diseases involving HDAC8 enzymatic activity.