• Proceeding of EDISON Challenge
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• 2016.03a
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• pp.90-95
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• 2016

Heat Shock 70kDa Protein 1-Like(HSPA1L)는 Heat-shock protein70(HSP70) family에 속하는 chaperone protein으로 polypeptide folding, assembly, protein degradation 등 다양한 biological processes에 관여하고 있다. HSPA1L은 human methyltransferase-like protein 21A(METTL21A)에 의해 lysine residue에 methylation이 일어나게 되는데, 암세포에서 일반적인 HSPA1L은 주로 세포질에서 발견되는 반면 methylated HSPA1L의 경우 주로 핵에서 발견이 됨으로써 HSPA1L methylation이 암 세포 성장에 중요할 역할을 할 것이라 추측되며 anti-cancer drug target으로 주목 받고 있다. 하지만 현재 HSPA1L의 구조가 부분적으로만 밝혀져 있어 HSPA1L와 METTL21A가 어떤 residue들이 interaction 하여 binding을 하는지에 대해서 아직 밝혀 지지 않았다. 이로 인해 anti-cancer drug target으로서의 연구에 제한이 있다. 이번 연구에서는 homology modeling(Galaxy-TBM, Galaxy-refine)을 통해 HSPA1L 전체 구조를 밝혀 낸 후, HSPA1L 와 METTL21A를 protein-protein docking을 통해 binding pose 예측을 하였다. 이러한 binding pose를 protein interaction analysis하여 HSPA1L과 METTL21A binding에 관여하는 중요 residue들을 밝혀 냈다. 이러한 structural information은 methylated HSPA1L와 암 세포 성장간의 연관성, 더 나아가 anti-cancer drug 개발로 까지도 이어 질 수 있을 것이라 생각한다.

• Genomics & Informatics
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• v.8 no.2
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• pp.70-75
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• 2010

Asp66his, Asp54Lys, and Asp50Asn are mutations in connexin 26 that are observed in the clinic and give rise to autosomal dominant syndromes. They are the result of point mutations in the human gap junction ${\beta}-2$ gene. In order to investigate the structural mechanism of Bart-Pumphrey Syndrome, Keratitis-Ichthyosis-Deafness Syndrome, and Vohwinkel Syndrome, homology modeling was carried out. Asp66 has direct contact with Asn62 by two hydrogen bonds in the wild-type protein, and in Asp66His, the biggest change observed is a tremendous energy increase caused by hydrogen bond breakage to Asn62. Shifts in the side chain and new hydrogen bond formation are observed for Lys54 compared to the wild-type protein (Asn54) and result in closer contact to Val84. Asp50Asn causes a significant decrease in bond energy, and residual charge reversal repels the ion and metabolites and, hence, inhibits their transportation. Such perturbations are likely to be a factor contributing to abnormal functioning of ion channels, resulting cell death and disease.

• Microbiology and Biotechnology Letters
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• v.47 no.2
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• pp.278-288
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• 2019

In the present investigation, we attempted to design a protocol to develop a hybrid protein with better bioremediation capacity. Using in silico approaches, a Hybrid Open Reading Frame (Hybrid ORF) is developed targeting the genes of microorganisms known for degradation of organophosphates. Out of 21 genes identified through BLAST search, 8 structurally similar genes (opdA, opd, opaA, pte RO, pdeA, parC, mpd and phnE) involved in biodegradation were screened. Gene conservational analysis categorizes these organophosphates degrading 8 genes into 4 super families i.e., Metallo-dependent hydrolases, Lactamase B, MPP and TM_PBP2 superfamily. Hybrid protein structure was modeled using multi-template homology modeling (3S07_A; 99%, 1P9E_A; 98%, 2ZO9_B; 33%, 2DXL_A; 33%) by $Schr{\ddot{o}}dinger$ software suit version 10.4.018. Structural verification of protein models was done using Ramachandran plot, it was showing 96.0% residue in the favored region, which was verified using RAMPAGE. The phosphotriesterase protein was showing the highest structural similarity with hybrid protein having raw score 984. The 5 binding sites of hybrid protein were identified through binding site prediction. The docking study shows that hybrid protein potentially interacts with 10 different organophosphates. The study results indicate that the hybrid protein designed has the capability of degrading a wide range of organophosphate compounds.

• Bulletin of the Korean Chemical Society
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• v.34 no.11
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• pp.3429-3443
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• 2013

Chemokine receptor (CCR2) is a G protein-coupled receptor that contains seven transmembrane helices. Recent pharmaceutical research has focused on the antagonism of CCR2 and candidate drugs are currently undergoing clinical studies for the treatment of diseases like arthritis, multiple sclerosis, and type 2 diabetes. In this study, we analyzed the time dependent behavior of CCR2 docked with a potent 4-azetidinyl-1-aryl-cyclohexane (4AAC) derivative using molecular dynamics simulations (MDS) for 20 nanoseconds (ns). Homology modeling of CCR2 was performed and the 4AAC derivative was docked into this binding site. The docked model of selected conformations was then utilized to study the dynamic behavior of the 4AAC enzyme complexes inside lipid membrane. MDS of CCR2-16b of 4AAC complexes allowed us to refine the system since binding of an inhibitor to a receptor is a dynamic process and identify stable structures and better binding modes. Structure activity relationships (SAR) for 4AAC derivatives were investigated and reasons for the activities were determined. Probable binding pose for some CCR2 antagonists were determined from the perspectives of binding site. Initial modeling showed that Tyr49, Trp98, Ser101, Glu291, and additional residues are crucial for 4AAC binding, but MDS analysis showed that Ser101 may not be vital. 4AAC moved away from Ser101 and the hydrogen bonding between 4AAC and Ser101 vanished. The results of this study provide useful information regarding the structure-based drug design of CCR2 antagonists and additionally suggest key residues for further study by mutagenesis.

• Journal of Integrative Natural Science
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• v.6 no.4
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• pp.205-210
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• 2013

Human P-gp is a protein responsible for the multidrug resistance (MDR) and causes failure of cancer chemotherapy. Till date no X-ray crystal structure is reported for this membrane protein, which hampers active research in the field. We performed homology modeling to develop three dimensional (3D) model of P-gp, and docking studies of the verapamil and curcumin have been performed to gain insight into the interaction mechanism between inhibitors and P-gp. It was identified that the inhibitors docked into the upper part of P-gp and interacted through the hydrophobic interactions.

• Bulletin of the Korean Chemical Society
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• v.33 no.3
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• pp.869-880
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• 2012

Identification of the selective chemical features for Aurora-B inhibitors gained much attraction in drug discovery for the treatment of cancer. Hence to identify the Aurora-B critical features various techniques were utilized such as pharmacophore generation, virtual screening, homology modeling, molecular dynamics, and docking. Top ten hypotheses were generated for Aurora-B and Aurora-A. Among ten hypotheses, HypoB1 and HypoA1 were selected as a best hypothesis for Aurora-B and Aurora-A based on cluster analysis and ranking score, respectively. Test set result revealed that ring aromatic (RA) group in HypoB1 plays an essential role in differentiates Aurora-B from Aurora-A inhibitors. Hence, HypoB1 used as 3D query in virtual screening of databases and the hits were sorted out by applying drug-like properties and molecular docking. The molecular docking result revealed that 15 hits have shown strong hydrogen bond interactions with Ala157, Glu155, and Lys106. Hence, we proposed that HypoB1 might be a reasonable hypothesis to retrieve the structurally diverse and selective leads from various databases to inhibit Aurora-B.

• Applied Biological Chemistry
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• v.41 no.8
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• pp.563-567
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• 1998

Computer aided molecular modeling can help to predict the three dimensional structure of the polypeptide without the sample. The study on soybean Bowman-Birk protease inhibitor (SBI) is valuable, because it has been recently known that SBI possesses anticarcinogenic activities and immune-stimulating properties. SBI has several isoinhibitors, whose isolation and characterization were reported in 1990. Among these, DII inhibits trypsin only. The different inhibitory specificities cannot be explained only by their different primary sequences, but is possible with further assistance by the study on their different three dimensional structures. The study on the three dimensional structure of DII using homology method is reported in this paper.

• Journal of Life Science
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• v.24 no.2
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• pp.128-136
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• 2014

Alginates are linear acidic polysaccharides composed with (1-4)-linked ${\alpha}$-L-guluronic acid and ${\beta}$-Dmannuronic acid. Alginate can be degraded by diverse alginate lyases, which cleave the alginate using a ${\beta}$-elimination reaction and produce unsaturated uronate oligomers. A gene for a polyMG-specific alginate lyase possessing a novel structure was previously identified and cloned from Stenotrophomonas maltophilia KJ-2. Homology modeling of KJ-2 polyMG-specific alginate lyase showed it belongs to the PL6 family, whereas three Azotobacter vinelandii polyMG lyases belong to the PL7 family of polysaccharide lyases. From $^1H$-NMR spectra data, KJ-2 polyMG lyase preferably degraded the M-${\beta}$(1-4)-G glycosidic bond than the G-${\alpha}$(1-4)-M glycosidic bond. Seventeen mutants were made by site-directed mutagenesis, and alginate lyase activity was analyzed. Lys220Ala, Arg241Ala, Arg241Lys, and Arg265Ala lost alginate lyase activity completely. Arg155Ala, Gly303Glu, and Tyr304Phe also lost the activity by 60.7-80.1%. These results show that Arg155, Lys220, Arg241, Arg265, Gly303, and Tyr304 are important residues for catalytic activity and substrate binding.

• Journal of agriculture & life science
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• v.46 no.4
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• pp.9-20
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• 2012

Eugenol is a volatile compound synthesized by eugenol synthase in various plants and belongs to phenylpropene compounds. However, characteristics of eugenol synthase in tomato has not been known. Therefore, we cloned a full length cDNA of a putative eugenol synthase from tomato 'Micro-Tom' using rapid amplification of cDNA ends (RACE) technique and named a clone SlEGS. Open reading frame of SlEGS was 921bp long and its deduced amino acid sequence was 307bp. The BLAST analysis indicated that SlEGS shared high similarity with PhEGS1 (67.1%) and CbEGS2 (69.4%). Amino acid composition of SlEGS was determined by CLC genomics workbench tool and 3D structure of SlEGS was constructed by homology modeling using Swiss-PDB viewer and validated using PROCHECK and ProSA-web tool. In addition, the physiochemical properties of SlEGS was evaluated using ExPASy's ProtParam tool. Molecular weight was 33.93kDa and isoelectric point was 5.85 showing acidic nature. Other properties such as extinction coefficient, instability index, aliphatic index, and grand average hydropathy was also analyzed.

• Applied Biological Chemistry
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• v.40 no.6
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• pp.597-599
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• 1997