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Molecular modelling to investigate tubulin conformational dynamics driven by antimitotic agents.

Valentina Ripa

Molecular modelling to investigate tubulin conformational dynamics driven by antimitotic agents.

Rel. Marco Agostino Deriu. Politecnico di Torino, Corso di laurea magistrale in Ingegneria Biomedica, 2019

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Abstract:

Microtubules (MT) play key roles in cell mitosis and in particular they help to segregate chromosomes. For this reason, MT are a desirable target in cancer treatment for the inhibition of the unregulated tumoral cells division. In addition, several tubulin isotypes exist, each one having its own sensitivity to a specific drug and a different level of expression depending on tissues. This represents an important opportunity in drug design, which exploits the isotypes expression to study and synthesize highly specific drugs, having a greater affinity only for diseased cells and causing reduced systemic effects. Antimitotic drugs act by interfering with MT polymerization-depolymerization kinetics, but the molecular mechanisms responsible for the drug activity is still unclear. These drugs can be classified according to their effects on MT dynamics. In this work, we have considered one stabilizing agent, i.e. taxol, and a destabilizing one, i.e. colchicine. More in detail, molecular modelling has been employed to investigate the effects of these drugs on the conformational behaviour expressed by two different human tubulin isotypes. Results of the present research might shed light on the molecular mechanism of action of investigated drugs and thus make clearer the induced tubulin conformational modifications which affect the entire MT dynamics.

Relators: Marco Agostino Deriu
Academic year: 2019/20
Publication type: Electronic
Number of Pages: 58
Subjects:
Corso di laurea: Corso di laurea magistrale in Ingegneria Biomedica
Classe di laurea: New organization > Master science > LM-21 - BIOMEDICAL ENGINEERING
Aziende collaboratrici: UNSPECIFIED
URI: http://webthesis.biblio.polito.it/id/eprint/12935
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