Computational Approaches to the Rational Design of Tubulin-Targeting Agents
Microtubules are highly dynamic polymers of α,β-tubulin dimers which play an essential role in numerous cellular processes such as cell proliferation and intracellular transport, making them an attractive target for cancer and neurodegeneration research. To date, a large number of known tubulin bind...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/2/285 |
| _version_ | 1797622159382675456 |
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| author | Helena Pérez-Peña Anne-Catherine Abel Maxim Shevelev Andrea E. Prota Stefano Pieraccini Dragos Horvath |
| author_facet | Helena Pérez-Peña Anne-Catherine Abel Maxim Shevelev Andrea E. Prota Stefano Pieraccini Dragos Horvath |
| author_sort | Helena Pérez-Peña |
| collection | DOAJ |
| description | Microtubules are highly dynamic polymers of α,β-tubulin dimers which play an essential role in numerous cellular processes such as cell proliferation and intracellular transport, making them an attractive target for cancer and neurodegeneration research. To date, a large number of known tubulin binders were derived from natural products, while only one was developed by rational structure-based drug design. Several of these tubulin binders show promising in vitro profiles while presenting unacceptable off-target effects when tested in patients. Therefore, there is a continuing demand for the discovery of safer and more efficient tubulin-targeting agents. Since tubulin structural data is readily available, the employment of computer-aided design techniques can be a key element to focus on the relevant chemical space and guide the design process. Due to the high diversity and quantity of structural data available, we compiled here a guide to the accessible tubulin-ligand structures. Furthermore, we review different ligand and structure-based methods recently used for the successful selection and design of new tubulin-targeting agents. |
| first_indexed | 2024-03-11T09:06:21Z |
| format | Article |
| id | doaj.art-d4f593ddf054481a8b5d47b16c72ba32 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T09:06:21Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-d4f593ddf054481a8b5d47b16c72ba322023-11-16T19:23:00ZengMDPI AGBiomolecules2218-273X2023-02-0113228510.3390/biom13020285Computational Approaches to the Rational Design of Tubulin-Targeting AgentsHelena Pérez-Peña0Anne-Catherine Abel1Maxim Shevelev2Andrea E. Prota3Stefano Pieraccini4Dragos Horvath5Department of Chemistry, Università degli Studi di Milano, Via Golgi 19, 20133 Milan, ItalyDepartment of Chemistry, Università degli Studi di Milano, Via Golgi 19, 20133 Milan, ItalyLaboratory of Chemoinformatics, Faculty of Chemistry, University of Strasbourg, 4, Rue Blaise Pascal, 67081 Strasbourg, FranceLaboratory of Biomolecular Research, Paul Scherrer Institute, Forschungsstrasse 111, 5232 Villigen, SwitzerlandDepartment of Chemistry, Università degli Studi di Milano, Via Golgi 19, 20133 Milan, ItalyLaboratory of Chemoinformatics, Faculty of Chemistry, University of Strasbourg, 4, Rue Blaise Pascal, 67081 Strasbourg, FranceMicrotubules are highly dynamic polymers of α,β-tubulin dimers which play an essential role in numerous cellular processes such as cell proliferation and intracellular transport, making them an attractive target for cancer and neurodegeneration research. To date, a large number of known tubulin binders were derived from natural products, while only one was developed by rational structure-based drug design. Several of these tubulin binders show promising in vitro profiles while presenting unacceptable off-target effects when tested in patients. Therefore, there is a continuing demand for the discovery of safer and more efficient tubulin-targeting agents. Since tubulin structural data is readily available, the employment of computer-aided design techniques can be a key element to focus on the relevant chemical space and guide the design process. Due to the high diversity and quantity of structural data available, we compiled here a guide to the accessible tubulin-ligand structures. Furthermore, we review different ligand and structure-based methods recently used for the successful selection and design of new tubulin-targeting agents.https://www.mdpi.com/2218-273X/13/2/285computer-aided drug designmicrotubulesmicrotubule targeting agentsvirtual screeningmolecular dockingmolecular dynamics simulations |
| spellingShingle | Helena Pérez-Peña Anne-Catherine Abel Maxim Shevelev Andrea E. Prota Stefano Pieraccini Dragos Horvath Computational Approaches to the Rational Design of Tubulin-Targeting Agents Biomolecules computer-aided drug design microtubules microtubule targeting agents virtual screening molecular docking molecular dynamics simulations |
| title | Computational Approaches to the Rational Design of Tubulin-Targeting Agents |
| title_full | Computational Approaches to the Rational Design of Tubulin-Targeting Agents |
| title_fullStr | Computational Approaches to the Rational Design of Tubulin-Targeting Agents |
| title_full_unstemmed | Computational Approaches to the Rational Design of Tubulin-Targeting Agents |
| title_short | Computational Approaches to the Rational Design of Tubulin-Targeting Agents |
| title_sort | computational approaches to the rational design of tubulin targeting agents |
| topic | computer-aided drug design microtubules microtubule targeting agents virtual screening molecular docking molecular dynamics simulations |
| url | https://www.mdpi.com/2218-273X/13/2/285 |
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