• Journal of the Korean Chemical Society
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• v.67 no.4
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• pp.226-235
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• 2023

Chikungunya fever has a high morbidity rate in humans and is caused by chikungunya virus. There are no treatments available until now for this particular viral disease. The present study was carried out by selecting 19 flavonoids, which are available naturally in fruits, vegetables, tea, red wine and medicinal plants. The molecular docking of selected 19 flavonoids was carried out against the Chikungunya virus capsid protein using the Autodock4.2 software. Binding affinity analysis based on the Intermolecular interactions such as Hydrogen bonding and hydrophobic interactions and drug-likeness properties for all the 19 flavonoids have been carried out and it is found that the top four molecules are Chrysin, Fisetin, Naringenin and Biochanin A as they fit to the chikungunya protein and have binding energy of -8.09, -8.01, -7.6, and 7.3 kcal/mol respectively. This result opens up the possibility of applying these compounds in the inhibition of chikungunya viral protein.

• 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.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2004.11a
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• pp.210-218
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• 2004

Poly(ADP-ribose)polymerase-1 (PARP-1) is a nuclear enzyme involved in various physical functions related to genomic repair, and PARP inhibitors have therapeutic application in a variety of neurological diseases. Docking and the QSAR (quantitative structure-activity relationships) studies for 52 PARP-1 inhibitors were conducted using FlexX algorithm, comparative molecular field analysis (CoMFA), and hologram quantitative structure-activity relationship analysis (HQSAR). The resultant FlexX model showed a reasonable correlation (r$^{2}$ = 0.701) between predicted activity and observed activity. Partial least squares analysis produced statistically significant models with q$^{2}$ values of 0.795 (SDEP=0.690, r$^{2}$=0.940, s=0.367) and 0.796 (SDEP=0.678, r$^{2}$ = 0.919, s=0.427) for CoMFA and HQSAR, respectively. The models for the entire inhibitor set were validated by prediction test and scrambling in both QSAR methods. In this work, combination of docking, CoMFA with 3D descriptors and HQSAR based on molecular fragments provided an improved understanding in the interaction between the inhibitors and the PARP. This can be utilized for virtual screening to design novel PARP-1 inhibitors.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.65.2-65.2
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• 2003

88 selective COX-2 inhibitors belonging to three chemical classes (triaryl rings, diaryl cycloalkanopyrazoles, and diphenyl hydrazides) were studied using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Partial least squares analysis produced statistically significant models with q values of 0.84 and 0.79 for CoMFA and CoMSIA, respectively. The key spatial properties were detected by careful analysis of the isocontour maps. The binding energies calculated from flexible docking correlated with inhibitory activities by the least-squares fit method. (omitted)

• Journal of the Korean Chemical Society
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• v.62 no.2
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• pp.106-112
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• 2018

Ice-binding proteins have an affinity for ice. They create a gap between the melting and freezing points by inhibiting the growth of ice, known as thermal hysteresis (TH). Interestingly, moderately active LeIBP and hyperactive FfIBP are almost identical in primary and tertiary structures, but differ in TH activity. The TH of FfIBP is tenfold higher than that of LeIBP, due to a subtle difference in their ice-binding motifs. To further evaluate the difference in TH, the interactions were investigated by ice-etching and molecular docking. Ice-etching showed that FfIBP binds to the primary and secondary prism, pyramidal, and basal planes; previously, LeIBP was found to bind to the basal and primary prism planes. Docking analysis using shape complementarity (Sc) showed that the hyperactive FfIBP had higher Sc values for all four ice planes than LeIBP, which is comparable with TH. Docking can be used to describe the hyperactivity of IBPs.

• Bulletin of the Korean Chemical Society
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• v.29 no.8
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• pp.1499-1504
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• 2008

Pyrazine derivatives bind to b-RAF receptor which is important in cancer therapy. The ligand-receptor interactions have been studied by comparative molecular field analysis (CoMFA) and molecular docking methods. Applying conventional ligand-based alignment schemes for the whole set was not successful. However, QM and DFT results suggested that some ligands have electrostatic interaction while others have steric interactions. On the basis of these results, we divided the dataset into two subsets. Electrostatic effect was found to be important in one set while steric effect for the other. Best docking modes were obtained for each subset based on the available crystal structure. These receptor-guided CoMFA models propose an interesting possibility which is difficult to obtain otherwise. i.e., in one binding mode the electrostatic interaction plays a key role for one subset ($q^2$ = 0.46, $r^2$ = 0.98), while in another binding mode steric effect is important with another subset ($q^2$ = 0.43, $r^2$ = 0.74).

• Journal of Integrative Natural Science
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• v.11 no.2
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• pp.121-129
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• 2018

CXCR6 is a major target in drug design as it is a determinant receptor in many diseases like AIDS, Type I Diabetes, some cancer types, atherosclerosis, tumor formation, liver disease and steatohepatitis. In this study, we propose the active site residues of CXCR6 molecule. We employed homology modelling and molecular docking approach to generate the 3D structure for CXCR6 and to explore its interaction between the antagonists and agonists. 3D models were generated using 14 different templates having high sequence identity with CXCR6. Surflex docking studies using pyridine and pyrimidine derivatives enabled the analysis of the binding site and finding of the important residues involved in binding. 3D structure of CXCL16, a natural ligand for CXCR6, was modelled using PHYRE and protein - protein docking was performed using ClusPro. The residues which were found to be crucial in interaction with the ligand are THR110, PHE113, TYR114, GLN160, GLN195, CYS251 and SER255. This study can be used as a guide for therapeutic studies of human CXCR6.

• Genomics & Informatics
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• v.13 no.2
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• pp.60-67
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• 2015

The leading cause of cancer mortality globally amongst the women is due to human papillomavirus (HPV) infection. There is need to explore anti-cancerous drugs against this life-threatening infection. Traditionally, different natural compounds such as withaferin A, artemisinin, ursolic acid, ferulic acid, (-)-epigallocatechin-3-gallate, berberin, resveratrol, jaceosidin, curcumin, gingerol, indol-3-carbinol, and silymarin have been used as hopeful source of cancer treatment. These natural inhibitors have been shown to block HPV infection by different researchers. In the present study, we explored these natural compounds against E6 oncoprotein of high risk HPV18, which is known to inactivate tumor suppressor p53 protein. E6, a high throughput protein model of HPV18, was predicted to anticipate the interaction mechanism of E6 oncoprotein with these natural inhibitors using structure-based drug designing approach. Docking analysis showed the interaction of these natural inhibitors with p53 binding site of E6 protein residues 108-117 (CQKPLNPAEK) and help reinstatement of normal p53 functioning. Further, docking analysis besides helping in silico validations of natural compounds also helped elucidating the molecular mechanism of inhibition of HPV oncoproteins.

• Genomics & Informatics
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• v.15 no.4
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• pp.142-146
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• 2017

More effective production of human insulin is important, because insulin is the main medication that is used to treat multiple types of diabetes and because many people are suffering from diabetes. The current system of insulin production is based on recombinant DNA technology, and the expression vector is composed of a preproinsulin sequence that is a fused form of an artificial leader peptide and the native proinsulin. It has been reported that the sequence of the leader peptide affects the production of insulin. To analyze how the leader peptide affects the maturation of insulin structurally, we adapted several in silico simulations using 13 artificial proinsulin sequences. Three-dimensional structures of models were predicted and compared. Although their sequences had few differences, the predicted structures were somewhat different. The structures were refined by molecular dynamics simulation, and the energy of each model was estimated. Then, protein-protein docking between the models and trypsin was carried out to compare how efficiently the protease could access the cleavage sites of the proinsulin models. The results showed some concordance with experimental results that have been reported; so, we expect our analysis will be used to predict the optimized sequence of artificial proinsulin for more effective production.

• Bulletin of the Korean Chemical Society
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• v.35 no.7
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• pp.2097-2108
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• 2014

Chemical feature based quantitative pharmacophore models were generated using the HypoGen module implemented in DS2.5. The best hypothesis, Hypo1, which was characterized by the highest correlation coefficient (0.96), the highest cost difference (61.60) and the lowest RMSD (0.74), consisted of one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic and one ring aromatic. The reliability of Hypo1 was validated on the basis of cost analysis, test set, Fischer's randomization method and GH test method. The validated Hypo1 was used as a 3D search query to identify novel inhibitors. The screened molecules were further refined by employing ADMET, docking studies and visual inspection. Three compounds with novel scaffolds were selected as the most promising candidates for the designing of Mcl-1 antagonists. Finally, a 10 ns molecular dynamics simulation was carried out on the complex of receptor and the retrieved ligand to demonstrate that the binding mode was stable during the MD simulation.