Data di Pubblicazione:
2023
Citazione:
Computational Approaches to the Rational Design of Tubulin-Targeting Agents / H. Pérez-Peña, A. Abel, M. Shevelev, A.E. Prota, S. Pieraccini, D. Horvath. - In: BIOMOLECULES. - ISSN 2218-273X. - 13:2(2023), pp. 285.1-285.35. [10.3390/biom13020285]
Abstract:
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
QSAR; computer-aided drug design; microtubule targeting agents; microtubules; molecular docking; molecular dynamics simulations; pharmacophore screening; virtual screening
Elenco autori:
H. Pérez-Peña, A. Abel, M. Shevelev, A.E. Prota, S. Pieraccini, D. Horvath
Link alla scheda completa:
Link al Full Text: