| KEYWORD |
Determination of the binding sites and binding modes of gatastatin and its novel derivatives
keywords GLIOBLASTOMA, TUBULIN, COMPUTATIONAL DRUG DISCOVERY
Reference persons MARCO AGOSTINO DERIU, JACEK ADAM TUSZYNSKI
Research Groups 28- biomedica
Thesis type COMPUTATIONAL
Description Glioblastoma multiforme (GBM) is a very aggressive brain tumor that lowers life expectancy of the patients to 15 months, which is why there is a great needs for an efficacious treatment. Treatment of this type of tumor often involves the use of chemotherapeutic drugs, many of which some target microtubules by blocking cell division. Currently used antimitotic drugs bind preferentially to the alpha/beta tubulin dimer, while gamma tubulin is a novel target for drug development for GBM. There have been several in silico studies aimed at finding inhibitors of gamma tubulin with Gatastatin being identified as a specific inhibitor of gamma tubulin but it also binds to beta tubulin, so it is urgently need to determine its primary cellular target. This is the main objective of this project, which will focus on computational studies of Gatastatin and its derivatives vis a vis binding to both beta and gamma tubulin. The student will use the software package called MOE as well as ADMET Predictor to determine the affinity of gatastatin for γ-tubulin and β-tubulin as well as its pharmacokinetic properties. Our collaborators in Poland (Dr. A. Gora at the Technical University of Silesia) will perform parallel experimental determination of the kd values for these compounds against both tubulin isotypes.
Required skills Molecular Dynamics simulations, docking and basic informatic and cheminformatic searches.
Deadline 26/02/2022
PROPONI LA TUA CANDIDATURA