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Area Engineering
Computational design of novel PROTAC structures targeting the KRAS pathway
Thesis abroad
keywords CONJUGATION, IN SILICO MODELING, PROTAC, RATIONAL
Reference persons MARCO AGOSTINO DERIU, JACEK ADAM TUSZYNSKI
External reference persons Prof. Richard Fahlman, Department of Biochemistry, University of Alberta, Edmonton, Canada.
Research Groups 28- biomedica
Thesis type COMPUTATIONAL
Description This project will involve computational design of a novel chemical entity, which will be constructed from a yet-to-be determined inhibitor of the KRAS pathway, a linker molecule and a new E3 ligase binding compound discovered earlier by Drs. Richard Fahlman and Jack Tuszynski at the University of Alberta. The student will generate a small combinatorial library of such constructs and simulate their stability in silico. The various structures will differ in the linker molecule lengths and attachment sites. Subsequent simulations will demonstrate which of the new entities preserve the binding activities to both KRAS and E3, respectively. Part of the activities planned in this project will take place at the University of Alberta, Canada, in collaboration with Drs. M. Aminpour (Department of Biomedical Engineering), R. Fahlamn (Department of Biochemistry) and an industrial partner, Dr. J. Yao of Hermay Pharmacueticals, which will perform chemical synthesis of the top ranked compounds.
Required skills familiarity with bioinformatics, computational drug design and molecular dynamics software.
Notes It is expected that the travel to the University of Alberta will take place in the period between January and June, 2022. However, given the uncertainty regarding the COVID situation the student may perform most or all of the research in Italy if travel is not allowed. At present, only doubly vaccinated students are allowed to enter the campus of the University of Alberta.
Deadline 15/10/2022
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