| KEYWORD |
Area Ingegneria
Computational analysis of the structural features of the family of FABP proteins
Parole chiave FABP FAMILY OF PROTEINS, MOLECULAR MODELING AND SIMULATION, PROTEINS, STRUCTURAL SIMILARITY
Riferimenti JACEK ADAM TUSZYNSKI
Gruppi di ricerca 28- biomedica
Tipo tesi COMPUTATIONAL
Descrizione The FABP family of proteins contains at least 12 members encoded by different genes. Numerous (over 20) atomic resolution structures of FABP exist in the Protein Data Bank (PDB) but they are from different FABPs and animal sources. This project will carry out sequence and structure similarity analysis for these proteins in Homo Sapiens. To do this, sequence alignment will be carried out and areas of similarities and differences identified. Following this, for those members of the FABP protein family whose structures have not been crystallographically resolved, we will use AI prediction methods, mainly alphafold (Nobel Prize in Chemistry 2024) to generate the most likely structures and superimpose them on one another to find out where similarities and differences occur, especially in functional domains and binding pockets. Then, molecular dynamics will be used to model multiple equilibrated states of the solvated proteins representing their range of flexibility in solution. We will accurately characterize protein-protein and protein-drug interactions, and perform binding free energy analysis using the MM/PBSA method and MM/GBSA method. The final outcome will be an identification of opportunistic structural features on the drug binding target, FABP12 protein, which have the greatest structural differences compared to the other proteins, which will be considered undesirable off-targets.
The student will be able to perform the tasks for the project in collaboration with a team of multi-disciplinary researchers at the University of Alberta in Edmonton, Canada. Part of the time dedicated to this project can be spent in Canada and both preliminary work and thesis writing can be done in Italy.
Conoscenze richieste basic skills at performing bioinformatic data analysis, database searches, familiarity with molecular modeling software, some computer coding may be necessary as well
Note The student will participate in online meetings with the Canadian team and once in Canada, take part in in-person meetings and discussions with the Canadian collaborators.
Scadenza validita proposta 16/10/2025
PROPONI LA TUA CANDIDATURA