A Computational Workflow for the Identification of Novel Fragments Acting as Inhibitors of the Activity of Protein Kinase CK1δ
| Autor: | Mattia Sturlese, Maicol Bissaro, Davide Bassani, Stephanie Federico, Eleonora Cescon, Stefano Moro, Giovanni Bolcato, Giampiero Spalluto, Matteo Pavan |
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| Přispěvatelé: | Bolcato, Giovanni, Cescon, Eleonora, Pavan, Matteo, Bissaro, Maicol, Bassani, Davide, Federico, Stephanie, Spalluto, Giampiero, Sturlese, Mattia, Moro, Stefano |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Fragment-based lead discovery Molecular Conformation Workflow Models Drug Discovery Biology (General) Vemurafenib Spectroscopy media_common protein kinase CK1δ Drug discovery Kinase molecular dynamic General Medicine Computer Science Applications Molecular Docking Simulation Chemistry Casein Kinase Idelta Casein kinase 1 fragment-based drug discovery medicine.drug Human Protein Binding Drug Gene isoform molecular docking molecular dynamics supervised molecular dynamics Binding Sites Humans Molecular Dynamics Simulation Protein Kinase Inhibitors Structure-Activity Relationship QH301-705.5 media_common.quotation_subject supervised molecular dynamic Protein Kinase Inhibitor Computational biology Biology Catalysis Article Inorganic Chemistry medicine Physical and Theoretical Chemistry Protein kinase A Molecular Biology QD1-999 Organic Chemistry Binding Site Molecular |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 18 International Journal of Molecular Sciences, Vol 22, Iss 9741, p 9741 (2021) |
| Popis: | Fragment-Based Drug Discovery (FBDD) has become, in recent years, a consolidated approach in the drug discovery process, leading to several drug candidates under investigation in clinical trials and some approved drugs. Among these successful applications of the FBDD approach, kinases represent a class of targets where this strategy has demonstrated its real potential with the approved kinase inhibitor Vemurafenib. In the Kinase family, protein kinase CK1 isoform δ (CK1δ) has become a promising target in the treatment of different neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. In the present work, we set up and applied a computational workflow for the identification of putative fragment binders in large virtual databases. To validate the method, the selected compounds were tested in vitro to assess the CK1δ inhibition. |
| Databáze: | OpenAIRE |
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