In Silico Identification of Potential Inhibitors of the Wnt Signaling Pathway in Human Breast Cancer
Autor: | Icaro Alves Pinto, Nelson José Freitas da Silveira |
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Rok vydání: | 2019 |
Předmět: |
Models
Molecular In silico Antineoplastic Agents Triple Negative Breast Neoplasms Ligands Wnt3 Protein 03 medical and health sciences 0302 clinical medicine Breast cancer Genetics medicine Humans Computer Simulation Molecular Biology Wnt Signaling Pathway 030304 developmental biology 0303 health sciences business.industry Wnt signaling pathway medicine.disease Frizzled Receptors Molecular Docking Simulation Computational Mathematics Computational Theory and Mathematics 030220 oncology & carcinogenesis Modeling and Simulation Cancer research Female Drug Screening Assays Antitumor business Human breast |
Zdroj: | Journal of computational biology : a journal of computational molecular cell biology. 27(7) |
ISSN: | 1557-8666 |
Popis: | Triple-negative breast cancer is the leading worldwide cause of cancer-related deaths in women. The prospection and development of new substances with antitumoral potential is of great importance for the treatment of this disease. The objective of this work was to identify a commercial drug or ligand that could potentially bind to the FZD7 transmembrane protein and inactivate the Wnt signaling pathway in triple-negative breast cancer cells. We aimed at computationally modeling the FZD7, Wnt3, and Wnt3a proteins, at making them available in protein model databases, and at conducting docking analysis to assess the binding free energy between FZD7 and the selected ligands. The Wnt3 and Wnt3a proteins were modeled by homology modeling, and the FZD7 protein was modeled by homology modeling and ab initio modeling. The ligands were selected based on their similarity to the palmitoleic acid and were gathered from the ZINC database. A total of 30 commercially available ligands were found in the ZINC database. The docking results show that the ligands zinc08221009, zinc13546050, zinc05260769, zinc04529321, and zinc05972969 are good candidates for novel drug development. The created models and conducted analysis by this work will most certainly help in future research on the Wnt signaling pathway and its components. |
Databáze: | OpenAIRE |
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