• Natural Product Sciences
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• v.27 no.2
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• pp.99-114
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• 2021

Type 2 diabetes mellitus (T2DM) and its complications are important noncommunicable diseases with high mortality rates. Protein tyrosine phosphatase 1B (PTP1B) and aldose reductase inhibitors are recently approached and advanced for T2DM and its complications therapy. Matricaria chamomilla L. is acknowledged as a worldwide medicinal herb that has many beneficial health effects as well as antidiabetic effects. Our research was designed to determine the most potential antidiabetic phytochemicals from M. chamomilla employing in silico study. 142 phytochemicals were obtained from the databases. The first screening employed iGEMdock and Swiss ADME, involving 93 phytochemicals. Finally, 30 best phytochemicals were docked. Molecular docking and visualization analysis were performed using Avogadro, AutoDock 4.2., and Biovia Discovery Studio 2016. Molecular docking results demonstrate that ligand-protein interaction's binding affinities were -5.16 to -7.54 kcal/mol and -5.30 to -12.10 kcal/mol for PTP1B and aldose reductase protein targets respectively. In silico results demonstrate that M. chamomilla has potential antidiabetic phytochemical compounds for T2DM and its complications. We recommended anthecotulide, quercetin, chlorogenic acid, luteolin, and catechin as antidiabetic agents due to their binding affinities against both PTP1B and aldose reductase protein. Those phytochemicals' significant efficacy and potential as antidiabetic must be investigated in further advanced research.

• Clinical and Experimental Vaccine Research
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• v.13 no.2
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• pp.146-154
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• 2024

Purpose: Infection by the intracellular apicomplexan parasite Toxoplasma gondii has serious clinical consequences in humans and veterinarians around the world. Although about a third of the world's population is infected with T. gondii, there is still no effective vaccine against this disease. The aim of this study was to develop and evaluate a multimeric vaccine against T. gondii using the proteins calcium-dependent protein kinase (CDPK)1, CDPK2, CDPK3, and CDPK5. Materials and Methods: Top-ranked major histocompatibility complex (MHC)-I and MHC-II binding as well as shared, immunodominant linear B-cell epitopes were predicted and linked using appropriate linkers. Moreover, the 50S ribosomal protein L7/L12 (adjuvant) was mixed with the construct's N-terminal to increase the immunogenicity. Then, the vaccine's physicochemical characteristics, antigenicity, allergenicity, secondary and tertiary structure were predicted. Results: The finally-engineered chimeric vaccine had a length of 680 amino acids with a molecular weight of 74.66 kDa. Analyses of immunogenicity, allergenicity, and multiple physiochemical parameters indicated that the constructed vaccine candidate was soluble, non-allergenic, and immunogenic, making it compatible with humans and hence, a potentially viable and safe vaccine candidate against T. gondii parasite. Conclusion: In silico, the vaccine construct was able to trigger primary immune responses. However, further laboratory studies are needed to confirm its effectiveness and safety.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8191-8196
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• 2016

Inhibition of EGFR-EGF interactions forms an important therapeutic rationale in treatment of non-small cell lung carcinoma. Established inhibitors have been successful in reducing proliferative processes observed in NSCLC, however patients suffer serious side effects. Considering the narrow therapeutic window of present EGFR inhibitors, the present study centred on identifying high efficacy EGFR inhibitors through structure based virtual screening strategies. Established inhibitors - Afatinib, Dacomitinib, Erlotinib, Lapatinib, Rociletinib formed parent compounds to retrieve similar compounds by linear fingerprint based tanimoto search with a threshold of 90%. The compounds (parents and respective similars) were docked at the EGF binding cleft of EGFR. Patch dock supervised protein-protein interactions were established between EGF and ligand (query and similar) bound and free states of EGFR. Compounds ADS103317, AKOS024836912, AGN-PC-0MXVWT, GNF-Pf-3539, SCHEMBL15205939 were retrieved respectively similar to Afatinib, Dacomitinib, Erlotinib, Lapatinib, Rociletinib. Compound-AGN-PC-0MXVWT akin to Erlotinib showed highest affinity against EGFR amongst all the compounds (parent and similar) assessed in the study. Further, AGN-PC-0MXVWT brought about significant blocking of EGFR-EGF interactions in addition showed appreciable ADMET properties and pharmacophoric features. In the study, we report AGN-PC-0MXVWT to be an efficient and high efficacy inhibitor of EGFR-EGF interactions identified through computational approaches.

• Genomics & Informatics
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• v.14 no.3
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• pp.112-124
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• 2016

Solid tumor is generally observed in tissues of epithelial or endothelial cells of lung, breast, prostate, pancreases, colorectal, stomach, and bladder, where several genes transcription is regulated by the microRNAs (miRNAs). Argonaute (AGO) protein is a family of protein which assists in miRNAs to bind with mRNAs of the target genes. Hence, study of the binding mechanism between AGO protein and miRNAs, and also with miRNAs-mRNAs duplex is crucial for understanding the RNA silencing mechanism. In the current work, 64 genes and 23 miRNAs have been selected from literatures, whose deregulation is well established in seven types of solid cancer like lung, breast, prostate, pancreases, colorectal, stomach, and bladder cancer. In silico study reveals, miRNAs namely, miR-106a, miR-21, and miR-29b-2 have a strong binding affinity towards PTEN, TGFBR2, and VEGFA genes, respectively, suggested as important factors in RNA silencing mechanism. Furthermore, interaction between AGO protein (PDB ID-3F73, chain A) with selected miRNAs and with miRNAs-mRNAs duplex were studied computationally to understand their binding at molecular level. The residual interaction and hydrogen bonding are inspected in Discovery Studio 3.5 suites. The current investigation throws light on understanding miRNAs based gene silencing mechanism in solid cancer.

• Journal of Integrative Natural Science
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• v.16 no.4
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• pp.123-131
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• 2023

Breast cancer continues to pose a substantial worldwide health challenge, thereby requiring the development of innovative strategies to discover new therapeutic interventions. Signal Transducer and Activator of Transcription 3 (STAT-3) has been identified as a significant factor in the development of several types of cancer, including breast cancer. This is primarily attributed to its diverse functions in promoting tumour formation and conferring resistance to therapeutic interventions. This study presents an in silico drug repositioning approach that focuses on identifying specific inhibitors of STAT-3 for the purpose of treating breast cancer. We initially examined the structural and functional attributes of STAT-3, thereby elucidating its crucial involvement in cellular signalling cascades. A comprehensive virtual screening was performed on a diverse collection of drugs that have been approved by the FDA from zinc15 database. Various computational techniques, including molecular docking, cross docking, and cDFT analysis, were utilised in order to prioritise potential candidates. This prioritisation was based on their predicted binding energies and outer molecular orbital reactivity. The findings of our study have unveiled a Dihydroergotamine and Paritaprevir that have been approved by the FDA and exhibit considerable promise as selective inhibitors of STAT-3. In conclusion, the utilisation of our in silico drug repositioning approach presents a prompt and economically efficient method for the identification of potential compounds that warrant subsequent experimental validation as selective STAT-3 inhibitors in the context of breast cancer. The present study highlights the considerable potential of employing computational strategies to expedite the drug discovery process. Moreover, it provides valuable insights into novel avenues for targeted therapeutic interventions in the context of breast cancer treatment.

• Journal of Life Science
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• v.28 no.2
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• pp.195-200
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• 2018

Beta-asarone is the well-known active ingredient of Rhizoma acori graminei. In this study, we investigated and compared the binding affinity of mosquito oviposition pheromone (MOP; (5R,6S)-6-acetoxy-5-hexadecanolide) and beta-asarone on the A domain of the mosquito odorant binding protein 1 (CquiOBP1) by in silico computational docking studies. The three-dimensional crystallographic structure of CquiOBP1 was obtained from the PDB database (PDB ID: 3OGN). In silico computational auto-docking analysis was performed using PyRx, Autodock Vina, Discovery Studio Version 4.5, and the NX-QuickPharm option based on scoring functions. The beta-asarone showed optimum binding affinity (docking energy) with CquiOBP1 as -6.40 kcal/mol as compared to the MOP (-6.00 kcal/mol). Among the interacting amino acids (LEU76, LEU80, ALA88, MET89, HIS111, TRP114, and TYR122), tryptophan 114 in the CquiOBP1 active site significantly interacted with both MOP and beta-asarone. Amino acids substitution (mutation) from non-polar groups to the polar (or charged) groups of the CquiOBP1 dramatically changed the X, Y, Z grid position and binding affinity of both ligands. These results significantly indicated that beta-asarone could be a more potent ligand to the CquiOBP1 than MOP. Therefore, the extract of Rhizoma acori graminei or beta-asarone can be applied to the fields of insecticidal and repellant biomaterial development.

• Journal of Life Science
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• v.28 no.4
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• pp.408-414
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• 2018

Actein is the well-known active ingredient of Cimicifugae rhizoma (Black cohosh). In this study, we investigated and compared the binding affinity of tubocurarine, actein, and actein derivatives on the B&C domain of the acetylcholine binding protein through in silico computational docking studies. The three-dimensional crystallographic structure of the acetylcholine binding protein B&C domain was obtained from the PDB database (PDB ID: 2XYT). An in silico computational autodocking analysis was performed using PyRx, Autodock Vina, Discovery Studio Version 4.5, and NX-QuickPharm based on scoring functions. The actein showed an optimum binding affinity (docking energy), with the acetylcholine binding protein at -10.50 kcal/mol as compared to the tubocurarine (-9.80 kcal/mol). The interacting amino acids tryptophan 84 and tryptophan 147, in the B domain of the acetylcholine binding protein active site, significantly interacted with the actein and 27-deoxyactein, and (26R)-actein. The centroid XYZ grid position of the tubocurarine was X=38.300689, Y=112.053467, and Z=51.991022, but the actein and its derivatives showed values around X=26.4, Y=127.3, Z=43.7. These results clearly indicated that actein and its derivatives could be a more potent antagonist to the acetylcholine binding protein than tubocurarine. Therefore, the extract of Cimicifugae rhizoma or actein containing biomaterials can substitute for the botulinum toxin-mediated acetylcholine receptor regulation, and be applied to the anti-wrinkle cosmetics industry.

• Toxicological Research
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• v.25 no.1
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• pp.9-15
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• 2009

Historically, research in toxicology has utilized non-human mammalian species, particularly rats and mice, to study in vivo the effects of toxic exposure on physiology and behavior. However, ethical considerations and the overwhelming increase in the number of chemicals to be screened has led to a shift away from in vivo work. The decline in in vivo experimentation has been accompanied by an increase in alternative methods for detecting and predicting detrimental effects: in vitro experimentation and in silico modeling. Yet, these new methodologies can not replace the need for in vivo work on animal physiology and behavior. The development of new, non-mammalian model systems shows great promise in restoring our ability to use behavioral endpoints in toxicological testing. Of these systems, the zebrafish, Danio rerio, is the model organism for which we are accumulating enough knowledge in vivo, in vitro, and in silico to enable us to develop a comprehensive, high-throughput toxicology screening system.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.55 no.4
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• pp.371-378
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• 2010

For sensitive and accurate gene expression analysis, normalization of gene expression data against housekeeping genes is required. There are conventional housekeeping gene (e.g. ACT) that primarily function as an internal control of transcription. In this study, we performed an in silico analysis of 278 rice gene expression samples (GSM) in order to identify the gene that is most consistently expressed. Based on this analysis, we identified novel candidate housekeeping genes that displayed improved stability among the cross experimental conditions. Furthermore four of the most conventional housekeeping genes were included in our 30 other housekeeping genes among the most stable genes. Therefore, these 30 genes can he used to normalize transcription results in gene expression studies on rice at a broad range of experimental conditions.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.10
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• pp.1473-1477
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• 2007

Four-and-a-half LIM-only protein 3 (FHL3) is a member of the LIM protein superfamily and can participate in mediating protein-protein interaction by binding one another through their LIM domains. In this study, the 5'- and 3'- cDNA ends were characterized by RACE (Rapid Amplification of the cDNA Ends) methodology in combination with in silico cloning based on the partial cDNA sequence obtained. Bioinformatics analysis showed FHL3 protein contained four LIM domains and four LIM zinc-binding domains. In silico mapping assigned this gene to the gene cluster MTF1-INPP5B-SF3A3-FHL3-CGI-94 on pig chromosome 6 where several QTL affecting intramuscular fat and eye muscle area had previously been identified. Transcription of the FHL3 gene was detected in spleen, liver, kidney, small intestine, skeletal muscle, fat and stomach, with the greatest expression in skeletal muscle. The A/G polymorphism in exon II was significantly associated with birth weight, average daily gain before weaning, drip loss rate, water holding capacity and intramuscular fat in a Landrace-derived pig population. Together, the present study provided the useful information for further studies to determine the roles of FHL3 gene in the regulation of skeletal muscle cell growth and differentiation in pigs.