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.

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]

Computational Approaches to the Rational Design of Tubulin-Targeting Agents

A. Abel
Secondo
;
S. Pieraccini
Penultimo
;
2023

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.
QSAR; computer-aided drug design; microtubule targeting agents; microtubules; molecular docking; molecular dynamics simulations; pharmacophore screening; virtual screening
Settore CHIM/02 - Chimica Fisica
   Tuning Tubulin Dynamics and Interactions to Face Neurotoxicity: a Multidisciplinary Approach for Training and Research
   TUBInTrain
   EUROPEAN COMMISSION
   860070 — TubInTrain — H2020-MSCA-ITN-2019
2023
Article (author)
File in questo prodotto:
File Dimensione Formato  
biomolecules-13-00285-v2.pdf

accesso aperto

Descrizione: Review
Tipologia: Publisher's version/PDF
Dimensione 4.07 MB
Formato Adobe PDF
4.07 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/956858
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 7
social impact