Novel hits for autosomal dominated polycystic kidney disease (ADPKD) targeting derived by
            <i>in silico</i>
            screening on ZINC-15 natural product database

Nejabat, Mojgan; Hadizadeh, Farzin; Nejabat, Masoud; Rajabi, Omid

doi:10.1080/07391102.2023.2196700

Cited by 3 publications

(3 citation statements)

References 46 publications

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“…When developing new alternative inhibitors, molecular docking could provide insight into the correct binding pocket and interaction mode of complexes but may not provide information on the energy contribution of each docking compound . Δ G of TcGclc-ZINC000032992384 and TcGclc-ZINC000003911041 showed lower binding free energy (−25.14 ± 0.17 and −22.41 ± 0.17 kcal/mol, respectively), which was more negative than that of TcGclc-BSO (−21.20 ± 0.24 kcal/mol) (Table ).…”

Section: Resultsmentioning

confidence: 99%

“…The final TcGclc model was used as the target protein. For further study, the TcGclc model was treated by the Prepare protein module in Discovery Studio 2019, and the putative BSO binding site was determined by the superimposition of the homologous Saccharomyces cerevisiae Gcs (ScGcs)–BSO cocrystal structure (PDB ID 3LVV) and prepared the binding sphere containing all the active residues using Define and Edit Binding Site module in Discovery Studio 2019. The prepared TcGclc protein model was used for all of the steps of virtual screening.…”

Section: Methodsmentioning

confidence: 99%

“…The molecular mechanics Poisson− Boltzmann surface area (MM/PBSA) is very widely used to calculate the binding free energy and contributions of polar and nonpolar energy in the complex system. 29 The MM/PBSA was used to calculate the binding free energies of TcGclc-ligand complexes (ΔG binding ) using gmx mmpbsa tool. 30 The energy contribution of each docking complex was estimated by ΔG binding which was calculated using the following equation:…”

Section: Free Energy Landscapementioning

confidence: 99%

See 2 more Smart Citations

Novel Inhibitor of Glutamate-Cysteine Ligase Catalytic Subunit against Tribolium castaneum: High-Throughout Virtual Screening, Molecular Docking and Dynamics Simulation, and Bioassay

Kim,

Chen,

et al. 2024

J. Agric. Food Chem.

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The enzyme glutamate-cysteine ligase catalytic subunit (Gclc) is a rate-limiting enzyme in the biosynthesis of glutathione that is involved in antioxidant defense, detoxification of xenobiotics, and/or its metabolites and regulates the cell cycle and immune function. Therefore, Gclc presents an appealing target for the development of novel insecticides. In this study, we conducted high-throughput virtual screening from the ZINC20 database and identified three compounds with high binding affinity to the Tribolium castaneum Gclc (TcGclc). Ultimately, we selected ZINC000032992384 due to its superior stability and lowest binding energy, as determined through molecular dynamics simulations. Bioassay results revealed that the IC 50 value of ZINC000032992384 was 19.70 μM lower than that of BSO (49.67 μM). Furthermore, the larval mortality in the ZINC000032992384 treated group was 63.8%, significantly higher than that of the controls (29.1% in the dichlorvos group and 6.4% in the acetone group). This study provides novel insights for the development of a Gclc-targeted inhibitor as a potent insecticide based on the interaction between receptors and ligands.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Free Energy Landscapementioning

confidence: 99%

See 1 more Smart Citation

Novel Inhibitor of Glutamate-Cysteine Ligase Catalytic Subunit against Tribolium castaneum: High-Throughout Virtual Screening, Molecular Docking and Dynamics Simulation, and Bioassay

Kim,

Chen,

et al. 2024

J. Agric. Food Chem.

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Identification of potent inhibitors targeting Tribolium castaneum GSTe2 via structure-based screening and molecular dynamics simulation

Kim,

Zhang,

Chen

et al. 2024

Journal of Biomolecular Structure and Dynamics

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The Application of Kinesin Inhibitors in Medical Issues

Nejabat,

Hadizadeh,

Sahebkar

2024

CRCEP

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Kinesins are a group of motor proteins in charge of several crucial functions in the cell. These proteins often bind to microtubules and perform their functions using the energy produced by ATP hydrolysis. One function of mitotic kinesin, a subclass of kinesin that is expressed during cell division at the mitotic phase, is to create the mitotic spindle. Uncontrolled cell growth is one trait of cancerous cells. Traditional anticancer medications still used in clinics include taxanes (paclitaxel) and vinca alkaloids (vincristine, vinblastine), which interfere with microtubule dynamics. However, because non-dividing cells like post-mitotic neurons contain microtubules, unwanted side effects like peripheral neuropathy are frequently found in patients taking these medications. More than ten members of the mitotic kinesin family play distinct or complementary roles during mitosis. The mitotic kinesin family's KSP, or Eg5, is regarded as its most dramatic target protein. The current work systematically reviews the use of kinesin inhibitors in the medical field. The challenges of KSP and the practical solutions are also examined, and the outcomes of the previous works are reported. The significant gaps and shortcomings of the related works are also highlighted, which can be an onset topic for future works.

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Novel hits for autosomal dominated polycystic kidney disease (ADPKD) targeting derived by in silico screening on ZINC-15 natural product database

Cited by 3 publications

References 46 publications

Novel Inhibitor of Glutamate-Cysteine Ligase Catalytic Subunit against Tribolium castaneum: High-Throughout Virtual Screening, Molecular Docking and Dynamics Simulation, and Bioassay

Novel Inhibitor of Glutamate-Cysteine Ligase Catalytic Subunit against Tribolium castaneum: High-Throughout Virtual Screening, Molecular Docking and Dynamics Simulation, and Bioassay

Identification of potent inhibitors targeting Tribolium castaneum GSTe2 via structure-based screening and molecular dynamics simulation

The Application of Kinesin Inhibitors in Medical Issues

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