• International Journal of Contents
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• 제9권4호
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• pp.11-15
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• 2013

"Protein Folding Problem" is considered to be one of the "Great Challenges of Computer Science" and prediction of disordered protein is an important part of the protein folding problem. Machine learning models can predict the disordered structure of protein based on its characteristic of "learning from examples". Among many machine learning models, we investigate the possibility of multilayer perceptron (MLP) as the predictor of protein disorder. The investigation includes a single hidden layer MLP, multi hidden layer MLP and the hierarchical structure of MLP. Also, the target node cost function which deals with imbalanced data is used as training criteria of MLPs. Based on the investigation results, we insist that MLP should have deep architectures for performance improvement of protein disorder prediction.

• International Journal of Industrial Entomology and Biomaterials
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• 제37권1호
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• pp.15-20
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• 2018

Most proteins produced in the endoplasmic reticulum (ER) of eukaryotic cells fold via disulfide formation (oxidative folding). Oxidative folding is catalyzed by protein disulfide isomerase (PDI) and PDI-related ER protein thiol disulfide oxidoreductases (ER oxidoreductases). In yeast and mammals, ER oxidoreductin-1s (ERO1s) supply oxidizing equivalent to the active centers of PDI. We previously identified and characterized the ERO1 of Bombyx mori (bERO1) as a thioredoxin-like protein that shares primary sequence homology with other ERO1s. Here we compare the reactivation of inactivated rRNase and sRNase by bERO1, and show that bERO1 and bPDI cooperatively refold denatured RNase A. This is the first result suggesting that bERO1 plays an essential role in ER quality control through the combined activities of bERO1 and bPDI as a catalyst of protein folding in the ER and sustaining cellular redox homeostasis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제50권4호
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• pp.177-188
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• 2024

The endoplasmic reticulum (ER) is crucial for protein synthesis, transport, and folding, as well as calcium storage, lipid and steroid synthesis, and carbohydrate metabolism. Endoplasmic reticulum stress (ERS) occurs when misfolded or unfolded proteins accumulate in the ER lumen due to increased protein secretion or impaired folding. While the role of ERS in disease pathogenesis has been widely studied, most research has focused on extraoral diseases, leaving the role of ERS in intraoral diseases unclear. This review examines the role of ERS in oral diseases and oral fibrosis pathogenesis. A systematic search of literature through July 2023 was conducted in the MEDLINE database (via PubMed) using specific terms related to ERS, oral diseases, and fibrosis. The findings were summarized in both table and narrative form. Emerging evidence indicates that ERS significantly contributes to the pathogenesis of oral diseases and fibrosis. ERS-induced dysregulation of protein folding and the unfolded protein response can lead to cellular dysfunction and inflammation in oral tissues. Understanding the relationship between ERS and oral disease pathogenesis could offer new therapeutic targets for managing oral health and fibrosis-related complications.

• Bulletin of the Korean Chemical Society
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• 제24권6호
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• pp.785-791
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• 2003

We have studied the folding mechanism of β-hairpins from proteins of 1GB1, 3AIT and 1A2P by unfolding simulations at high temperatures. The analysis of trajectories obtained from molecular dynamics simulations in explicit aqueous solution suggests that the three β-hairpin structures follow different mechanism of folding. The results of unfolding simulations showed that the positions of the hydrophobic core residues influence the folding dynamics. We discussed the characteristics of different mechanisms of β-hairpin folding based on the hydrogen-bond-centric and the hydrophobic-centric models.

• Bulletin of the Korean Chemical Society
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• 제29권4호
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• pp.741-748
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• 2008

We have studied the folding mechanism of $\beta$ -hairpins in the proteins 1GB1, 3AIT and 1A2P by conducting unfolding simulations at moderately high temperatures. The analysis of trajectories obtained from molecular dynamics simulations in explicit aqueous solution suggests that the positions of the hydrophobic core residues lead to subtle differences in the details of folding dynamics. However, the folding of three different hairpins can be explained by a unified mechanism that is a blend of the hydrogen-bond-centric and the hydrophobiccentric models. The initial stage of $\beta$-hairpin folding involves various partially folded intermediate structures which are stabilized by both the van der Waals interactions of hydrophobic core residues and the electrostatic interactions of non-native hydrogen bonds. The native structure is obtained by forming native contacts in the final tune-up process. Depending on the relative positions of the hydrophobic residues, the actual mechanism of hairpi n folding may or may not exhibit well-defined intermediates.

• Molecules and Cells
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• 제46권6호
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• pp.348-350
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• 2023

• BMB Reports
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• 제32권6호
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• pp.521-528
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• 1999

The folding of recombinant hepatitis B virus X-protein (rHBx) solubilized from Escherichia coli inclusion bodies was investigated. By sequential dialysis of urea, rHBx was folded into its native structure, which was demonstrated by the efficacy of its transcriptional activation of the adenovirus major late promoter (MLP), fluorescence spectroscopy, and circular dichroism (CD) analysis. The decrease in CD values at 220 nm and a corresponding blue shift of the intrinsic fluorescence emission confirmed the ability of rHBx to refold in lower concentrations of urea, yielding the active protein. Equilibrium and kinetic studies of the refolding of rHBx were carried out by tryptophan fluorescence measurements. From the biphasic nature of the fluorescence curves, the existence of stable intermediate states in the renaturation process was inferred. Reverse phase-high performance liquid chromatography (RP-HPLC) analysis further demonstrated the existence of these intermediates and their apparent compactness.

• Journal of Microbiology and Biotechnology
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• 제27권3호
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• pp.507-513
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• 2017

Bacillus subtilis spores can be used for protein display to engineer protein properties. This method overcomes viability and protein-folding concerns associated with traditional protein display methods. Spores remain viable under extreme conditions and the genotype/phenotype connection remains intact. In addition, the natural sporulation process eliminates protein-folding concerns that are coupled to the target protein traveling through cell membranes. Furthermore, ATP-dependent chaperones are present to assist in protein folding. CotA was optimized as a whole-cell biocatalyst immobilized in an inert matrix of the spore. In general, proteins that are immobilized have advantages in biocatalysis. For example, the protein can be easily removed from the reaction and it is more stable. The aim is to improve the pH stability using spore display. The maximum activity of CotA is between pH 4 and 5 for the substrate ABTS (ABTS = diammonium 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate). However, the activity dramatically decreases at pH 4. The activity is not significantly altered at pH 5. A library of approximately 3,000 clones was screened. A E498G variant was identified to have a half-life of inactivation ($t_{1/2}$) at pH 4 that was 24.8 times greater compared with wt-CotA. In a previous investigation, a CotA library was screened for organic solvent resistance and a T480A mutant was found. Consequently, T480A/E498G-CotA was constructed and the $t_{1/2}$ was 62.1 times greater than wt-CotA. Finally, E498G-CotA and T480A/E498G-CotA yielded 3.7- and 5.3-fold more product than did wt-CotA after recycling the biocatalyst seven times over 42 h.

• Bulletin of the Korean Chemical Society
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• 제35권6호
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• pp.1713-1719
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• 2014

1FSD is a 28-residue designed protein with a ${\beta}{\beta}{\alpha}$ motif. Since this protein displays most essential features of protein structures in such a small size, this model protein can be an outstanding system for evaluating the balance in the propensity of the secondary structures and the quality of all-atom protein force fields. Particularly, this protein would be difficult to fold to its correct native structure without establishing proper balances between the secondary structure elements in all-atom energy functions. In this work, a series of the recently optimized five amber protein force fields [$ff03^*$, $f99sb^*$-ildn, ff99sb-${\phi}^{\prime}$-ildn, ff99sb-nmr1-ildn, ff99sb-${\Phi}{\Psi}$(G24, CS)-ildn] were investigated for the simulations of 1FSD using a conventional molecular dynamics (MD) and a biased-exchange meta-dynamics (BEMD) methods. Among those tested force fields, we found that ff99sb-nmr1-ildn and ff99sb-${\Phi}{\Psi}$(G24, CS)-ildn are promising in that both force fields can locate the native state of 1FSD with a high accuracy (backbone rmsd ${\leq}1.7{\AA}$) in the global free energy minimum basin with a reasonable energetics conforming to a previous circular dichroism (CD) experiment. Furthermore, both force fields led to a common set of two distinct folding pathways with a heterogeneous nature of the transition state to the folding. We anticipate that these force fields are reasonably well balanced, thereby transferable to many other protein folds.

• Bulletin of the Korean Chemical Society
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• 제29권11호
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• pp.2172-2182
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• 2008