Estudi de la interacció entre l’EGF i el seu receptor EGFR per a crear lligands modificats i fer teràpia dirigida contra el cáncer

Abstract

Cancer is a worldwide known disease that affects a big part of the population, reason why it’s being studied nowadays in biomedical research. The tyrosine kinase receptors family ErbB is highly studied in cancer therapy, due to its implication in cell proliferation and differentiation pathways. The epidermal growth factor (EGF) is a ligand of this family that binds to its receptor EGFR causing a dimerization and consequently autophosphorylation, driving to the activation of the signaling path. Targeted cancer therapy it’s about guiding a drug to the tumoral cells through determined proteins (usually receptors) involved in the tumoral process. The idea of this project is to address the attack to the epidermal growth factor receptor (EGFR), which is involved in the uncontrolled massive cell proliferation characteristic of this disease, and lock it with a derivative of its own EGF ligand. To convert this ligand into a blocker agent is necessary to do some modifications to the residues that composes it, with the intention of maintain the natural affinity of this peptide to its receptor but avoiding that this causes dimerization, eluding the activation of the cell growth pathway. This final degree work is focused in the study of the natural interaction between the EGF ligand and its EGFR receptor, comparing it with the truncated model (EGFt) done by Panosa et al. in 2013. By molecular dynamics the trajectories of both models are generated and after analyzed by Amber16. Finally, docking of proteins is done by ClusPro 2.0 to foresee the interaction that would be between the modified ligands (EGFm) and the receptor