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Theses

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2022 - 20233
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Subject: Bioinformatics × Start date: 2022 × Type: Thesis ×
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    ThesisItemOpen Access
    In-silico identification of phytochemicals as potential agents to inhibit the growth of pests
    (CCSHAU, Hisar, 2023-05) Gahalyan, Dushyant; Panwar, Anil
    Compounds known as phytochemicals have a specific biological effect against pests. Insect molting and metamorphosis are controlled by ecdysteroids and the juvenile hormone. The natural hormone responsible for molting in the majority of insects, 20-hydroxyecdysone (20E), binds to and activates the ecdysone receptor (EcR), a heterodimer made up of two nuclear receptor proteins. EcR is an attractive target for safer and more targeted pesticides since compounds that act on it exclusively harm insects and other arthropods. Farmers mainly rely on quick pest management strategies to defend crops from pest attacks, primarily synthetic insecticides. Overuse and abuse of synthetic pesticides can have harmful effects on people, the environment, and non-target animals, which reduces biodiversity. Some toxic pesticides that could be extremely detrimental to mammals or the environment are aldicarb, malathion, parathion, etc. Many crop pests and human ailments have been successfully controlled by plants that produce bioactive compounds. High-throughput screening technologies have been created to effectively look for novel chemicals that interfere with the insect endocrine system. These methods will support the creation of ecdysone agonists that are particular for insect orders like Lepidoptera, Diptera, or Coleoptera's EcRs. The two receptors that were complexed with ligands were employed in this work to estimate binding affinity and predict binding mode. The potential orientation of a ligand with respect to a protein target can be determined extremely effectively using molecular docking. In this study, 93 phytochemical agents are docked against the main receptor of Heliothis virescens, and Bemisia tabaci. Five-five candidates are selected according to their high binding affinity for each insect, i.e. Helitohis Virescens (1R1K) and Bemisia tabaci (1Z5X). It is observed that for 1Z5X (Uscharin, Meliantriol, Campesterol, Daturaolone, and Epoxyazadiradione, which had binding affinities of -13.61, -13.28, -13.26, -12.29 and -12.24, respectively) were selected and for 1R1K (Campesterol, Azadirone, Uzarigenin, Meliantriol, and Pyrethrin-2 which had binding affinities of -13.12, -11.48, -9.94, -9.84 and -9.37, respectively) were selected. According to molecular dynamics simulation (20ns) investigations of the selected compounds, the top five docked 1R1K and 1Z5X compounds appear to have strong stability, flexibility, and binding affinity for ecdysone receptors.
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    ThesisItemOpen Access
    Computational studies of cytochrome P450 (CYPs) enzyme in pulses
    (CCSHAU, Hisar, 2023-10) Pooja; Ahalawat, Navjeet
    Cytochrome P450 (CYP450) is a large superfamily of enzymes found in all domains of life, including plants. It plays a crucial role in the metabolism of various compounds, including drugs, toxins, and endogenous substrates. Pulses are the richest source of fiber and complex carbohydrates, resulting in a low GI food. CYP450s enzymes are heme-containing monooxygenases that catalyze metabolisms of various endogenous and exogenous compounds. They constitute a superfamily of enzymes present in various organisms including mammals, plants, bacteria, and insects. CYP450s are diverse and metabolize a wide variety of substrates, but their structures are largely conserved. In this study, bioinformatics analyses of CYP450s enzyme performed in pulses. According to the conserved motifs obtained by MEME and MAST tools, ten motifs were common in all those pulses. The structural and functional analyses of CYP450s in pulses were done by using UniProtKB and InterProScan tools in ExPASy database. The tertiary structures of pulses were predicted by Phyre2 web server. The protein sequences were aligned with ClustalW and then the phylogenetic tree was constructed by MEGA11 using the neighbor-joining (NJ) method. By the successful analysis of CYP450s, we developed a productive database by using MYSQL and PHP. The database provides information related to 200 proteins of P450s in pulses with their predicted 3D structure in PDB format, functions and Fasta sequences. A Pulses Cytochrome P450 database serves as a centralized repository for curated information on CYP450 enzymes in pulses. It consolidates data from various sources, including sequence information, structural data, substrate specificity, and catalytic properties.
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    ThesisItemOpen Access
    Computational analysis of potential phytochemicals interaction with COVID-19 main protease
    (CCSHAU Hisar, 2022-07) Nisha; Ahalawat, Navjeet
    The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2020 has affected almost every country with around 543 million confirmed cases worldwide. Currently to fight against the infection, multiple vaccines and several types of drugs alone or with combination have been used in many countries for emergency use. Some severe side effects of repositioned drugs are a cause for concern and their efficacy is still under evaluation. Antiviral therapeutics based on phytochemicals that have been reported to have more tolerable side effects can serve as a reliable alternative to synthetic antiviral drugs for the inhibition of viral replication and penetration. The main protease of SARS-CoV-2 is one of the highly potent and vital targets to design and develop antiviral drugs for the inhibition of COVID-19 contamination. Computational approach helps to identified many drugs that can target viral proteins Mpro. We generated a phytochemical library containing 2453 phytochemicals which have been reported as having antiviral activity through deep literature study.The virtual molecular docking results reveals that five bioactive compounds; theaflavate C, theaflavin-3,3-O-digallate, amentoflavone, hinokiflavone, theaflavin3-gallate have a higher binding affinity toward COVID-19 main protease (MPro) with the binding energy of -10.1, -9.9, -9.7, -9.7 and -9.7 Kcal/mol. But these phytochemicals didn’t follow Lipinski rule of five, so we selected more four phytochemicals having ADMET properties. The main protease docked complexes with phytochemicals; theaflavate C, theaflavin-3,3-O-digallate, amentoflavone, hinokiflavone, theaflavin3-gallate, 10-methoxycamptothecin, caribine, sesamin and licoisoflavanone were used for MD simulation of 20 ns time period using Gromacs package. The MD results were analysed with respect to RMSD, RMSF, Rg, SASA, hydrogen bond and principal component analysis. The resulting trajectories of converged period of MD were further exploited in MM-P/G/BSA calculations to derive accurate estimates of binding free energies. The study provides a basic foundation and suggests that the seven phytochemicals, viz. theaflavate C, theaflavin-3,3-O-digallate, amentoflavone, hinokiflavone, theaflavin3-gallate, caribine, and licoisoflavanone serve as potential inhibitors in regulating the Mpro protein’s function and controlling viral replication and may assist the development of effective anti-COVID-19 drugs.