Project

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Winter 2022 challenge: rejected after 3 months

Designing PROTACs Binding Selectively the γ-tubulin Leading to its Degradation.

Fabiano Altieri, Polytechnic of Turin (Italy) - University of Alberta (Canada), Turin, Italy

PROteolysis TArgeting Chimeras aim to accelerate the degradation rate of the protein of interest (POI) by keeping it and E3 ligase close together for as long as possible. In this way, the ubiquitination is accelerated, and the proteasome finally degrades the POI. The main advantage, which is impossible to achieve with inhibitory drugs, is the possibility of using any compound, even biologically inert ones, that binds to any part of the surface of the POI and E3 ligase. My work aims to design a PROTAC to degrade selectively the γ-tubulin (γT), one of the central proteins involved in Microtubule nucleation. It is particularly over-expressed in Glioblastoma Multiforme. The idea is to us HYDE to obtain docking scores of train, test and valid sets to train deep neural network models (DNN). The DNN will reduce the multi-billion compounds database. In the end, FastGrow will optimize the ligand in the γT pocket. Parallelly, FlexX is used to compare the results with the previous way.
Fabiano intends to achieve the following milestones:
  1. Designing the warhead
  2. Designing the E3 ligand and linker
  3. Checking the effectivness of the designed PROTAC