Supervisors info:
Ηλίας Ηλιόπουλος (Επιβλέπων), Καθηγητής, Τμήμα Βιοτεχνολογίας, Γεωπονικό Πανεπιστήμιο Αθηνών
Κωνσταντίνος Βοργιάς, Καθηγητής, Τμήμα Βιολογίας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Βασιλική Οικονομίδου, Επίκουρη Καθηγήτρια, Τμήμα Βιολογίας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Summary:
In this diploma thesis several Lactate Dehydrogenase A inhibitors of the cancer cell, were studied, so as the pharmaceutical compounds that will contribute to the inhibition of the cancer cell to be found.
Initially, all the LDH-A structures from the Protein Data Bank (PDB) database ,were found and the structure with the best resolution was selected, in order to be used in the study.
Then, a spatial chains’ superposition of the selected structure was made and by this way the most representive chain in which the majority of LDH-A ligands had been linked, was found. Except from this first part, the diploma thesis includes three more parts.
In the first part, the ligands that existed in the LDH-A structures, were studied. More specifically, a docking of LDH-A ligands in the selected LDH-A binding site, via Autodock Vina, was made, so as the interaction sites between ligand and protein to be found.
In the second part, a set of compounds - LDH-A inhibitors from the BindingDB database, was used. In this part, the same methodology with the first part was followed, so as the methodology and software reliability, which were used, to be confirmed.
In the third part, three different groups of candidate drugs, in which anticancer compounds, cancer compounds and natural products were respectively included, were used. The methodology that was used in order the compounds which act suppressively to be found, was the same with the one of the two first parts.
All the compounds from the third part of docking that gave solution, will be used as possible targets against cancer cells. At this point, it has to be mentioned that, imaging visibility diagrams of the binding site – for all the compounds of the three docking parts that gave solution in the LDH-A binding site – via the program LIGPLOT, were made and the crucial LDH-A amino residues that take part in the interactions between LDH-A and compounds (ligands / inhibitors), were found.
Finally, as far as the compounds from the third part of docking are concerned, bibliographical data from PUBCHEM database which were related to their therapeutic action against several forms of cancer, were found.
