• CELLMED
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• v.6 no.4
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• pp.24.1-24.4
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• 2016

The emergence of influenza virus and antigenic drift are potential cause of world-wide pandemic. There are some commercially available drugs in the market to treat influenza. During past decade, however, critical resistances have been raised for biological targets. Because of structural complexity and flexibility of target proteins, applying a computational modeling tool is very beneficial for developing alternative anti-influenza drugs. In this review, we introduced molecular dynamics (MD) simulations approach to reflect full conformational flexibility of proteins during molecular modeling works. Case studies of MD works were summarized for the drug discovery and drug resistance mechanism of anti-influenza pharmaceuticals.

• KSBB Journal
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• v.21 no.4
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• pp.279-285
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• 2006

We investigated the effects of immobilization chemistry on the yield of immobilization and the bioactivity of the immobilized enzymes. Trypsin as a model protein and macroporous polymer beads(Toyopearl AF 650M, Tosho Co., Japan) was used as a model matrix. Four methods were used to immobilize trypsin; covalent conjugation by reductive amination(at pH 10.0 and pH 4.0) and affinity interaction via streptavidin-biotin, and double-affinity interaction via biotin-streptavidin-biotin system. The covalent conjugation immobilized $3{\sim}4$ mg/ml-gel, ca. 3-fold higher than the affinity method. However, the specific activity of the covalently(pH 10.0) and affinity-immobilized trypsin(via streptavidin-biotin) are ca. 37% and 50%, respectively, of that of the soluble enzyme(on the low-molecular-weight BAPNA substrate). When the molecular size of a substrate increased, the affinity-immobilized trypsin showed higher clavage activity on insulin and BSA. This result seemed to indicate the streptavidin-biotin system allowed more steric flexibility of the immobilized trypsin in its interaction with a substrate molecule. To confirm this, we studied the molecular flexibility of immobilized trypsin using quartz crystal microbalance-dissipation. Self-assembled monolayers were formed on the Q-sensor surface by aminoalkanethiols, and gultaraldehyde was attached to the SAMs. Trypsin was immobilized in two ways: reductive amination(at pH 10.0) and the streptavidin-biotin system. The dissipation shift of the affinity-immobilized trypsin was $0.8{\times}10^{-6}$, whereas that of the covalently attached enzyme was almost zero. This result confirmed that the streptavidin-biotin system allowed higher molecular flexibility. These results suggested that the bioactivity of the immobilized enzyme be strongly dependent on its molecular flexibility.

• Archives of Pharmacal Research
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• v.25 no.1
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• pp.11-24
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• 2002

The antitumor antibiotic (+)-CC-1065 can alkylate N3 of guanine in certain sequences. A previous high-field $^1H$ NMR study on the$(+)-CC-1065d[GCGCAATTG*CGC]_2$ adduct ($^*$ indicates the drug alkylation site) showed that drag modification on N3 of guanine results in protonation of the cross-strand cytosine [Park, H-J.; Hurley, L. H. J. Am. Chem. Soc.1997, 119,629]. In this contribution we describe a further analysis of the NMR data sets together with restrained molecular dynamics. This study provides not only a solution structure of the (+)-CC-1065(N3- guanine) DNA duplex adduct but also new insight into the molecular basis for the sequence- specific interaction between (+)-CC-1065 and N3-guanine in the DNA duplex. On the basis of NOESY data, we propose that the narrow minor groove at the 7T8T step and conformational kinks at the junctions of 16C17A and 18A19T are both related to DNA bending in the drugDNA adduct. Analysis of the one-dimensional $^1H$ NMR (in $H_2O$) data and rMD trajectories strongly suggests that hydrogen bonding linkages between the 8-OH group of the (+)-CC-1065 A-sub-unit and the 9G10C phosphate via a water molecule are present. All the phenomena observed here in the (+)-CC-1065(N3-guanine) adduct at 5'$-AATTG^*$are reminiscent of those obtained from the studies on the (+)-CC-1065(N3-adenine) adduct at $5'-AGTTA^*$, suggesting that (+)-CC-1065 takes advantage of the conformational flexibility of the 5'-TPu step to entrap the bent structure required for the covalent bonding reaction. This study reveals a common molecular basis for (+)-CC-1065 alkylation at both $5'-TTG^*$ and $5'-TTA^*$, which involves a trapping out of sequence-dependent DNA conformational flexibility as well as sequence-dependent general acid and general base catalysis by duplex DNA.

• KSBB Journal
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• v.31 no.4
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• pp.291-299
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• 2016

In this study, Indomethacin, the poorly water soluble drug, was selected and prepared dispersing oral disintegrating films according to the molecular weight of polyethylene glycol (PEG) which are sort of dispersing agents. Also the molecular weight and content of PEG were evaluated effect on the degree of dispersion, physical property and dissolution when making oral dispersing film containing indomethacin to find appropriate condition and suggested guidelines of making oral dispersing film. The appropriate dispersing ratio of the amount of surfactants and dispersing agent were 1% and 4%, also the stability dropped in the PEG molecular weight of 4000 or more. Drying time of oral dispersing film was $90^{\circ}C$ for 10 minutes to 12 minutes that dispersing film's property about flexibility, detachability were very good. The oral dispersion film's content used PEG 400 was $98.6{\pm}0.5%$ and the most uniform. As the molecular weight of PEG increased, dissolution time also increased. On the basis of evaluation parameter, PEG with 400~600 of molecular weight was selected as good dispersing agent in oral dispersing film. Therefore, it can be suggested guideline of preparation application study in oral dispersing film.

• Journal of Microbiology and Biotechnology
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• v.7 no.3
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• pp.200-203
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• 1997

Bacteria isolated from ultrapure water made by a high-purity water manufacturing system in a semiconductor manufacturing plant were classified into two groups which either grew in diluted nutrient broth medium (oligotrophic bacteria) or could not grow (copiotrophic bacteria). The nutritional flexibility of oligotrophic and copiotrophic bacteria was investigated. The oligotrophic bacteria were shown to be able to utilize a significantly broader range of organic substrates than the copiotrophic bateria. This finding substantiates the hypothesis that nutritional flexibility is adaptive for oligotrophic bacteria.

• Proceedings of the Zoological Society Korea Conference
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• 1996.10a
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• pp.267.2-267
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• 1996

No Abstract, See Full Text

• Proceedings of the Korean Vacuum Society Conference
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• 2011.02a
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• pp.114-114
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• 2011

We report a high-performance and air-stable flexible and invisible semiconductor which can be substitute for the n-type organic semiconductors. N-type organic-inorganic nanohybrid superlattices were developed for active semiconducting channel layers of thin film transistors at low temperature of $150^{\circ}C$ by using molecular layer deposition with atomic layer deposition. In these nanohybrid superlattices, self-assembled organic layers (SAOLs) offer structural flexibility, whereas ZnO inorganic layers provide the potential for semiconducting properties, and thermal and mechanical stability. The prepared SAOLs-ZnO nanohybrid thin films exhibited good flexibility, transparent in the visible range, and excellent field effect mobility (> 7cm2/$V{\cdot}s$) under low voltage operation (from -1 to 3V). The nanohybrid semiconductor is also compatible with pentacene in p-n junction diodes.

• Korean Chemical Engineering Research
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• v.49 no.1
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• pp.62-68
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• 2011

In the study, acrylate copolymer as MMA-co-GMA-co-AA with a high hardness and flexibility was synthesized for applying to the clear protection film, where GMA was used as a mediator to enhance polymerization-efficiency between MMA and AA. With an increase of GMA content, molecular weight and hardness of acrylate copolymer increased, however, flexibility decreased. With an increase of AA content, its molecular weight and hardness decreased, however, flexibility increased. Molar ratio of GMA/MMA and AA/GMA were optimized as 1.6 and 1.8, respectively, at 30 g of MMA to enhance hardness and flexibility of acrylate copolymer film. Molecular weight and Tg of the acrylate copoylmer were 13,300 g/mol and 136.5 $^{\circ}C$, respectively. Hardness of the coated film at 1.4 g/$m^2$ of spread was 1 H and no crack was observed at expansion ratio of 5% and 15%, respectively. Hardness of film was improved to 3 H by increasing spread of 4.1-4.6 g/$m^2$.

• Journal of Integrative Natural Science
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• v.7 no.2
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• pp.75-78
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• 2014

Computer-aided drug design uses computational chemistry to discover, enhance, or study drugs and related biologically active molecules. It is now proved to be effective in reducing costs and speeding up drug discovery. In this short review, we discussed on the importance of combining molecular docking and molecular dynamics simulation methodologies. We also reviewed the importance of protein flexibility, refinement of docked complexes using molecular dynamics and the use of free energy calculations for the calculation of accurate binding energies has been reviewed.

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.886-889
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• 2001

C-terminus specific immobilization often results in a increased structural stability resistant to various denaturation factors. In order to elucidate the immobilization effect on the c-terminus in molecular level, we made over 200 protein data set from Protein Data Bank(PDB), analyzed c-terminus structure of each protein, and investigated the structural relationship with the stabilizing factors such as hydrogen bond, ion pairs, cation pi, disulfide bond, solvation free energy, surface area, flexibility and so on.