| KEYWORD |
Computational modeling of fibronectin and a search for small molecule inhibitors of its interactions with integrins
keywords EXTRACELLULAR MATRIX PROTEINS, FIBRONECTIN, INTEGRIN, MOLECULAR DOCKING, MOLECULAR DYNAMICS, RATIONAL DRUG DESIGN
Reference persons MARCO AGOSTINO DERIU, JACEK ADAM TUSZYNSKI
External reference persons Dr. Maral Aminpour, Department of Biomedical Engineering, University of Alberta, Edmonton, Canada
Research Groups 28- biomedica
Thesis type COMPUTATIONAL
Description Fibronectin (FN) is a high-molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fragments of this large protein have been crystallized and these structures are available from the Protein Data Bank (PDB). The student will attempt to create a computational model of the entire protein by using homology modeling of the uncrystallized fragments of FN and splicing together with the crystallized domain. This will be followed by equilibration using molecular dynamics. The ultimate objective is to find the binding modes of the known inhibitors of FN and, using chemical similarity searches, identify new small molecule inhibitors of the FN-integrin interaction. The PDB entry 7NWL will be the starting point for these searches. The final result will include the identification of a pharmacophore for the inhibition of the FN-integrin interaction.
Required skills bioinformatics, chemi-informatics, molecular dynamics, docking, rational drug design
Notes Part of this project may take place at the University of Alberta, Edmonton, Canada but this is not a necessary condition. Travel to Canada is possible but it depends on the COVID situation, which changes on a daily basis.
Deadline 26/09/2022
PROPONI LA TUA CANDIDATURA