• Title/Summary/Keyword: Molecular dynamic

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Directed Evolution in Protein Functionality Improvement (단백질 기능 향상을 위한 방향적 진화)

  • 강환구;김학성
    • KSBB Journal
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    • v.16 no.2
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    • pp.107-114
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    • 2001
  • The dynamic evolution process has resulted in the myriad shapes, functions, and systems evident in every living organism. For centuries, people have been harnessing the power of evolution to produce new varieties of plants and animals, such as producing tomatoes from berries and Chihuahuas from wolves. Now scientists are using it to produce better molecules, ranging from drugs to industrial chemicals, and doing it in days or weeks rather than eons. The ingenious process, which creates genetic diversity and selects those with desired features in the laboratory, is called directed evolution or test tube evolution. In this paper, concepts of directed molecular evolution and some examples will be discussed.

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Juxtacrine regulation of cellular senescence

  • Narita, Masashi
    • BMB Reports
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    • v.52 no.1
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    • pp.3-4
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    • 2019
  • Cellular senescence is defined as a state of stable cell cycle exit in response to various stimuli, which include both cytotoxic stress and physiological cues. In addition to the core non-proliferative aspect, senescence is associated with diverse functionalities, which contribute to the role of senescence in a wide range of pathological and physiological processes. Such functionality is often mediated by the capability of senescent cells to communicate with their surroundings. Emerging evidence suggests that senescence is not a single entity, but a dynamic and heterogeneous collective phenotype. Understanding the diverse nature of senescence should provide insights into the complexity of tissue homeostasis and its disruption, such as in aging and tumorigenesis.

Epigenetic aspects of telomeric chromatin in Arabidopsis thaliana

  • Lee, Won Kyung;Cho, Myeon Haeng
    • BMB Reports
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    • v.52 no.3
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    • pp.175-180
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    • 2019
  • Telomeres are nucleoprotein complexes at the physical ends of linear eukaryotic chromosomes. They protect the chromosome ends from various external attacks to avoid the loss of genetic information. Telomeres are maintained by cellular activities associated with telomerase and telomere-binding proteins. In addition, epigenetic regulators have pivotal roles in controlling the chromatin state at telomeres and subtelomeric regions, contributing to the maintenance of chromosomal homeostasis in yeast, animals, and plants. Here, we review the recent findings on chromatin modifications possibly associated with the dynamic states of telomeres in Arabidopsis thaliana.

A Classical Molecular Dynamics Study of the Mg2+ Coordination in Todorokite (토도로카이트 내 Mg2+ 배위구조에 대한 고전분자동력학 연구)

  • Kim, Juhyeok;Lee, Jin-Yong;Kwon, Kideok D.
    • Journal of the Mineralogical Society of Korea
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    • v.32 no.3
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    • pp.151-162
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    • 2019
  • Todorokite, a tunnel-structured manganese oxide, can contain cations within the relatively large nanopores created by the $3{\times}3$ Mn octahedra. Because todorokite is poorly crystalline and found as aggregates mixed with other phases of Mn oxides in nature, the coordination structure of cations in the nanopores is challenging to fully characterize in experiment. In the current article, we report the atomistic coordination structures of $Mg^{2+}$ ions in todorokite tunnel nanopores using the classical molecular dynamics (MD) simulations. In experiment, $Mg^{2+}$ is known to occupy the center of the nanopores. In our MD simulations, 60 % of $Mg^{2+}$ ions were located at the center of the nanopores; 40 % of the ions were found at the corners. All $Mg^{2+}$ located at the center formed the six-fold coordination with water molecules, just as the ion in bulk aqueous solution. $Mg^{2+}$ ions at the corners also formed the six-fold coordination with not only water molecules but also Mn octahedral surface oxygens. The mean squared displacements were calculated to examine the dynamic features of $Mg^{2+}$ ions in the one-dimensional (1D) nanopores. Our MD simulations indicate that the dynamic features of water molecules and the cations observed in bulk aqueous solution are lost in the 1D nanopores of todorokite.

Enhanced Drug Carriage Efficiency of Curcumin-Loaded PLGA Nanoparticles in Combating Diabetic Nephropathy via Mitigation of Renal Apoptosis

  • Asmita Samadder;Banani Bhattacharjee;Sudatta Dey;Arnob Chakrovorty;Rishita Dey;Priyanka Sow;Debojyoti Tarafdar;Maharaj Biswas;Sisir Nandi
    • Journal of Pharmacopuncture
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    • v.27 no.1
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    • pp.1-13
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    • 2024
  • Background: Diabetic nephropathy (DN) is one of the major complications of chronic hyperglycaemia affecting normal kidney functioning. The ayurvedic medicine curcumin (CUR) is pharmaceutically accepted for its vast biological effects. Objectives: The Curcuma-derived diferuloylmethane compound CUR, loaded on Poly (lactide-co-glycolic) acid (PLGA) nanoparticles was utilized to combat DN-induced renal apoptosis by selectively targeting and modulating Bcl2. Methods: Upon in silico molecular docking and screening study CUR was selected as the core phytocompound for nanoparticle formulation. PLGA-nano-encapsulated-curcumin (NCUR) were synthesized following standard solvent displacement method. The NCUR were characterized for shape, size and other physico-chemical properties by Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS) and Fourier-Transform Infrared (FTIR) Spectroscopy studies. For in vivo validation of nephro-protective effects, Mus musculus were pre-treated with CUR at a dose of 50 mg/kg b.w. and NCUR at a dose of 25 mg/kg b.w. (dose 1), 12.5 mg/kg b.w (dose 2) followed by alloxan administration (100 mg/kg b.w) and serum glucose levels, histopathology and immunofluorescence study were conducted. Results: The in silico study revealed a strong affinity of CUR towards Bcl2 (dock score -10.94 Kcal/mol). The synthesized NCUR were of even shape, devoid of cracks and holes with mean size of ~80 nm having -7.53 mV zeta potential. Dose 1 efficiently improved serum glucose levels, tissue-specific expression of Bcl2 and reduced glomerular space and glomerular sclerosis in comparison to hyperglycaemic group. Conclusion: This study essentially validates the potential of NCUR to inhibit DN by reducing blood glucose level and mitigating glomerular apoptosis by selectively promoting Bcl2 protein expression in kidney tissue.

Characterization of the Alzheimer's disease-related network based on the dynamic network approach (동적인 개념을 적용한 알츠하이머 질병 네트워크의 특성 분석)

  • Kim, Man-Sun;Kim, Jeong-Rae
    • Journal of the Korean Institute of Intelligent Systems
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    • v.25 no.6
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    • pp.529-535
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    • 2015
  • Biological networks have been handled with the static concept. However, life phenomena in cells occur depending on the cellular state and the external environment, and only a few proteins and their interactions are selectively activated. Therefore, we should adopt the dynamic network concept that the structure of a biological network varies along the flow of time. This concept is effective to analyze the progressive transition of the disease. In this paper, we applied the proposed method to Alzheimer's disease to analyze the structural and functional characteristics of the disease network. Using gene expression data and protein-protein interaction data, we constructed the sub-networks in accordance with the progress of disease (normal, early, middle and late). Based on this, we analyzed structural properties of the network. Furthermore, we found module structures in the network to analyze the functional properties of the sub-networks using the gene ontology analysis (GO). As a result, it was shown that the functional characteristics of the dynamics network is well compatible with the stage of the disease which shows that it can be used to describe important biological events of the disease. Via the proposed approach, it is possible to observe the molecular network change involved in the disease progression which is not generally investigated, and to understand the pathogenesis and progression mechanism of the disease at a molecular level.

Quantitative Profiling of Dual Phosphorylation of Fus3 MAP Kinase in Saccharomyces cerevisiae

  • Hur, Jae-Young;Kang, Gum-Yong;Choi, Min-Yeon;Jung, Jin Woo;Kim, Kwang-Pyo;Park, Sang-Hyun
    • Molecules and Cells
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    • v.26 no.1
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    • pp.41-47
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    • 2008
  • Mitogen-activated protein kinase (MAPK) signaling is a crucial component of eukaryotic cells; it plays an important role in responses to extracelluar stimuli and in the regulation of various cellular activities. The signaling cascade is evolutionarily conserved in the eukaryotic kingdom from yeast to human. In response to a variety of extracellular signals, MAPK activity is known to be regulated via phosphorylation of a conserved $T{\times}Y$ motif at the activation loop in which both threonine and tyrosine residues are phosphorylated by the upstream kinase. However, the mechanism by which both residues are phosphorylated continues to remain elusive. In the budding yeast, Saccharomyces cerevisiae, Fus3 MAPK is involved in the mating signaling pathway. In order to elucidate the functional mechanism of MAPK activation, we quantitatively profiled phosphorylation of the $T{\times}Y$ motif in Fus3 using mass spectrometry (MS). We used synthetic heavy stable isotope-labeled phosphopeptides and nonphosphopeptides corresponding to the proteolytic $T{\times}Y$ motif of Fus3 and accompanying data-dependent tandem MS to quantitatively monitor dynamic changes in the phosphorylation events of MAPK. Phosphospecific immunoblotting and the MS data suggested that the tyrosine residue is dynamically phosphorylated upon stimulation and that this leads to dual phosphorylation. In contrast, the magnitude of threonine phosphorylation did not change significantly. However, the absence of a threonine residue leads to hyperphosphorylation of the tyrosine residue in the unstimulated condition, suggesting that the threonine residue contributes to the control of signaling noise.

Nitrogen을 도핑시킨 Ge-Sb-Te 박막의 광전자 및 광흡수 분광학 연구

  • Sin, Hyeon-Jun;Jeong, Min-Cheol;Kim, Min-Gyu;Lee, Yeong-Mi;Kim, Gi-Hong;Jeong, Jae-Gwan;Song, Se-An;Sun, Zhimei
    • Proceedings of the Korean Vacuum Society Conference
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    • 2013.02a
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    • pp.186-186
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    • 2013
  • Nitrogen doped Ge-Sb-Te (N-GST) thin films for phase change random access memory (PRAM) applications were investigated by synchrotron-radiation-based x-ray photoelectron spectroscopy and absorption spectroscopy. Nitrogen doping in GST resulted in more favorable N atoms' bonding with Ge atoms rather than with Sb and Te atoms [1,2], which explains the higher phase change transition temperature than that of undoped Ge-Sb-Te thin film. Surprisingly, it was noticed that N atoms also existed in the form of molecular nitrogen, $N_2$, which is detrimental to the stability of the GST performance [3]. N-doped GST experimental features were also supported by ab-initio molecular dynamic calculations [2]. References [1] M.-C. Jung, Y. M. Lee, H.-D. Kim, M. G. Kim, and H. J. Shin, K. H. Kim, S. A. Song, H. S. Jeong, C. H. Ko, and M. Han, "Ge nitride formation in N-doped amorphous Ge2Sb2Te5", Appl. Phys. Lett. 91, 083514 (2007). [2] Zhimei Sun, Jian Zhou, Hyun-Joon Shin, Andreas Blomqvist, and Rajeev Ahuja, "Stable nitride complex and molecular nitrogen in N doped amorphous Ge2Sb2Te5", Appl. Phys. Lett. 93, 241908 (2008). [3] Kihong Kim, Ju-Chul Park, Jae-Gwan Chung, and Se Ahn Song, Min-Cherl Jung, Young Mi Lee, Hyun-Joon Shin, Bongjin Kuh, Yongho Ha, Jin-Seo Noh, "Observation of molecular nitrogen in N-doped Ge2Sb2Te5", Appl. Phys. Lett. 89, 243520 (2006).

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$^{15}$N NMR Relaxation Study of the Catalytic Residues in Y14F Mutant Ketosteroid Isomerase

  • Yoon, Ye-Jeong;Lee, Hyeong-Ju;Kim, Chul;Lee, Hee-Cheon
    • Journal of the Korean Magnetic Resonance Society
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    • v.8 no.2
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    • pp.77-85
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    • 2004
  • $^1$H-detected $^{15}$N NMR was employed to investigated the effect of mutation (Y14F) on the dynamic properties of catalytic residues in ${\Delta}^5$-3- ketosteroid isomerase (KSI) from Conamonas testosteroni. In particular, the backbone dynamics of the catalytic residues have been studied in free enzyme and its complex with a steroid ligand, 19-nortestosterone hemisuccinate, by $^{15}$N relaxation measurements. The relaxation data were analyzed using the model-free formalism to extract the model-free parameters (S$^2$, ${\tau}_e$, and R$_{ex}$). The results show that the mutation causes a significant decrease in the order parameter (S$^2$) for the catalytic residues of free Y14F KSI, presumably due to breakdown of the hydrogen bond network by mutation. In addition, the order parameters of Phe-14 and Asp-99 increased slightly upon ligand binding, indicating a slight restriction of the high-frequency (pico- to nanosecond) internal motions of the residues in the complexed Y14F KSI, while the order parameter of Tyr-55 decreased significantly upon ligand binding.

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Comparision of the Properties of UV-cured Polyurethane Acrylates Containing Different Diisocyanates and Low Molecular Weight Diols

  • Yoo, Hye-Jin;Lee, Young-Hee;Kwon, Ji-Yun;Kim, Han-Do
    • Fibers and Polymers
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    • v.2 no.3
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    • pp.122-128
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    • 2001
  • UV-curable polyurethane acrylate prepolymers were prepared from diisocyanates [isophorone diisocyanate (IPDI), 2,4-toluene diisocyanate (TDI), or 4,4'-dicyclohexylmethane diisocyanate (H$_{12}$MDI)], diols [ethylene glycol (EG), 1,4-butane diol (BD), or 1,6-hexane diol (HD)], polypropylene glycol as a polyol. UY-curable mixtures were formulated from the prepolymer (90 wt%), reactive diluent monomer trimethylol propane triacrylate (10 wt%). and photoinitiator 1-hydroxycy-clohexyl ketone (3 wt% based on prepolymer/diluent). The effects of different diisocyanates/low molecular weigh dial on the dynamic mechanical thermal properties and elastic recovery of UV-cured polyurethane acrylate films were examined. The tensile storage modulus increased a little in the order of EG > BD > HD at the same diisocyanate. Two loss modulus peaks for all samples are observed owing to the glads transition of softs segments ($T_gh$) and the glass transition temperature of hard segments ($T_gh$). For the same diisocyanate, $T_gh$, decreased, however, $T_gh$ increased, in the order of HD > BD > EG. The elastic recovery also increased in the order of HD > BD > EG at the same diisocyanate. In case of same diols, $T_gh$ increased in the order of $H_12$MDl > TDI > IPDI significantly. The ultimate elongation and elastic recovery increased in the order of TDI > IPDI > $H_12$MDl at the same diol.l.

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