Botany - Research Publications

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/32

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End date: 2017Subject: search.filters.subject.Molecular Docking

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Now showing 1 - 4 of 4
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    Homology modeling of chemokine CCR7, molecular docking, and in vitro studies evidenced plausible immunotherapeutic anticancer natural compounds
    (Birkhauser Boston, 2016) Singh, Pushpendra; Singh, Ravi Shankar; Rani, Alka; Bast, Felix
    The chemokine receptor 7 is a G-protein coupled, receptors coordinates the migration of cancer cells towards CCL19 and CCL21 constitutively expressed lymphatic organs. Chemokine receptor 7 facilitates cancer progression by generating new lymphatic vessels that serve as conduits for tumor dissemination to lymph nodes. In this context, chemokine receptor 7 inhibitor recently caught an attention for cancer cell growth inhibitor. The 3-D crystalline structure of chemokine receptor 7 not available in protein data bank (PDB), first we predicted the 3-D structure of chemokine receptor 7 and then performed receptor-based molecular docking of chemokine receptor 7 against natural and marine compounds. Semiquantitative polymerase chain reaction (PCR) and quantitative real-time PCR were performed for mRNA expression of chemokine receptor 7 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) used as internal control. The best-docked compounds have been selected for chemokine receptor 7 inhibitors by optimal energy value (Gscore), types of interactions, and conformations. CID6441009, 42607750, 72276, 6711419, 56835050, 65064, 23663412, 72277, 643668, 54679285 compound have a better binding energy ?11.35, ?10.51, ?10.16, ?9.98, ?9.95, ?9.86, ?9.83, ?9.57, ?9.47, and ?9.45 respectively against chemokine receptor 7. Protein?ligand interactions profile highlighted that amino acid Glu45, Lys50, Arg54, Lys57, Trp114, Met260, Glu205, Gln227, Gln276, and Asp309 involved in the hydrophobic, hydrogen bonding, and ?-? stacking interactions play a central role at the active site. Moreover, treatment with the Epigallocatechin gallate led to down-regulation of mRNA expression of chemokine receptor 7 in HepG2 and PC3 cells. This molecular docking study recapitulates the docking free energy, protein?ligands interactions profile, pharmacokinetic, and the pharmacodynamic parameter of lead molecules, which are extremely helpful to improve the activity of natural and marine compounds against chemokine receptor 7. ? 2016, Springer Science+Business Media New York.
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    Screening and biological evaluation of myricetin as a multiple target inhibitor insulin, epidermal growth factor, and androgen receptor; In silico and in vitro
    (Springer New York LLC, 2015) Singh, Pushpendra; Bast, Felix
    Myricetin is a naturally omnipresent benzo-?-pyrone flavonoids derivative; has potent anticancer activity. Receptor tyrosine kinases family provides the decisive role in cancer initiation and progression. These receptors have recently caught the attention of the researchers as an attractive target to combat cancer, owing to the evidences endorsed their over-expression on cancer cells. This study is a concerted effort to explore the potent and specific multi-targeted inhibitor against RTKs and AR\ER employing molecular docking approach. IR, IGF1R, EGFR, VEGFR1, VEGFR2, and AR\ER were chosen as a protein and natural compounds as a ligand. Molecular docking procedure followed by using Maestro 9.6 (Schr?dinger Inc). All natural compounds were docked with the X-ray crystal structures of selected proteins by employing grid-based ligand docking with energetics Maestro 9.6. IBS natural compounds docked with each selected protein molecules by using GLIDE high throughput virtual screening. On the basis of Gscore, we selected 20 compounds from IBS (50,000 compounds) along with 68 anticancer compounds from published literature for GLIDE extra precision molecular docking. Calculated docking free energy yielded the excellent dock score for the myricetin when docked with proteins EGFR, IR, and AR\ER. Protein-ligand interactions profile highlighted that the lipophilic, hydrogen bonding and ?-? stacking interactions play a central role in protein-ligand interactions at the active site. The results of MTT assay reveal that the myricetin inhibit the viability and proliferation of cancer cells in a dose-dependent manner. Treatment with the myricetin led to down-regulation of mRNA expression of EGFR, IR, mTOR, and Bcl-2. Although, further in vitro and in vivo experimental studies are required for the experimental validation of our findings. ? 2015 Springer Science+Business Media New York.
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    Ganoderic acid targeting multiple receptors in cancer: in silico and in vitro study
    (Springer Netherlands, 2016) Gill, Balraj Singh; Navgeet; Kumar, Sanjeev; Gill, B.S.; Navgeet, Kumar, S.
    Receptor tyrosine kinases (RTKs) are transmembrane high-affinity surface receptors responsible for cell migration, adhesion, apoptosis, metabolism, and cell proliferation activities in various cancers. Minute aberration in the RTK signaling modulates the downstream signaling pathways that results in cancer. Ganoderic acid is a triterpene isolated from Ganoderma lucidum, which is renowned for its therapeutics effect, especially in cancer. The present study discusses receptor-based molecular docking of insulin receptor (IR), insulin-like growth factor receptor 1 (IGFR-1), vascular endothelial growth factor receptor-1 (VEGFR-1), vascular endothelial growth factor receptor-2 (VEGFR-2), and estrogen receptor (ER) with 50 isoforms of ganoderic acid along with natural inhibitors. These receptors were assessed for toxicity (ADMET) by using Maestro 9.6 (Schr?dinger Inc). The calculated docking free energy yielded an excellent dock score for the ganoderic acid when docked with proteins IR, IGFR-1, VEGFR-1, VEGFR-2, and ER, suggesting its potential in combating cancer. Protein?ligand profile highlighted the binding interactions comprising lipophilic, hydrogen bonding, pi-pi stacking interactions, and noncovalent bonding which play a pivotal role in targeting cancer. In silico studies revealed structure of ganoderic acid A as best isoforms among 50 isoforms which exhibits biological activity in liver cancer cells. Ganoderic acids A significantly decrease the viability, proliferation, and oxidative stress in a dose-dependent manner in liver cancer cells. ? 2016, International Society of Oncology and BioMarkers (ISOBM).
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    Ganoderic acid targeting nuclear factor erythroid 2–related factor 2 in lung cancer
    (Sage, 2017) Gill, Balraj Singh; Kumar, Sanjeev; Navgeet
    Lung cancer causes huge mortality worldwide, and targeting new pathway may provide an alternative in modulating signaling in cancer. Nuclear factor erythroid 2–related factor 2 is the major regulator of endogenous and exogenous stress by activating numerous antioxidant genes critical in cancer, Alzheimer’s, Parkinson’s, and inflammatory bowel diseases. Ganoderic acid is a triterpene from basiodiomycetes fungus Ganoderma lucidum with numerous therapeutic effects. In this study, ganoderic acid and its 50 isomers and natural activators were docked by receptor-based molecular docking using Maestro 9.6 (Schrödinger Inc.) in the Kelch-like ECH-associated protein 1-nuclear factor erythroid 2–related factor 2 signaling pathway. The receptor-based molecular docking reveals the best binding interaction of nuclear factor erythroid 2–related factor 2 and ganoderic acid A with GScore (−9.69) (kcal/mol), Lipophilic EvdW (−1.83), Electro (−0.72), Glide emodel (−73.369), H bond (−1.1), molecular mechanics/generalized Born surface area (−75.541) with Leu 718, Asp 800, Cys 797 residues involved in hydrogen bonding. The calculated docking energy highlights the lipophilic, hydrogen bonding, pi–pi stacking interactions, and non-covalent bonding. Analysis showed the involvement of cysteine and serine residues which were crucial in the activation and translocation from cytoplasm to the nucleus in the nuclear factor erythroid 2–related factor 2 signaling process. The molecular docking tool QikProp analyzed the absorption, distribution, metabolism, excretion, and toxicity but needs some modifications in their structure to satisfy Lipinski’s rule. Ganoderic acid A is a best docked isoform which inhibits the cell proliferation, viability, migration, and reactive oxygen species and messenger RNA expression of nuclear factor erythroid 2–related factor 2 in H460 cells.