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X-ray crystallography of biological macromolecules: advanced methods and applications |
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Teachers |
Prof. Filomena Sica (This email address is being protected from spambots. You need JavaScript enabled to view it.) Prof. Antonello Merlino (This email address is being protected from spambots. You need JavaScript enabled to view it.) |
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Credits (planned) |
2 |
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Planned hours |
16 |
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Planned schedules |
End of September contact Prof. Sica and Prof. Merlino to arrange the detailed timetable |
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Objectives |
The aim of this course is to provide an overview of the fundamental approach and the latest developments of X-ray crystallography of biological macromolecules. Examples of studies on structure-function relationship and of studies on the elucidation of complexes with ligands will be provided. |
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Description |
Crystallography is one of the most powerful techniques for the structural analysis at the atomic level. It has come to play an increasingly critical role in the drug discovery process and in understanding the molecular basis of many human diseases. In recent years, an increasingly important contribution to structural elucidation of bio-macromolecules and to understanding of their mechanisms of action has been obtained by electron microscopy at cryogenic conditions (Cryo-EM). This methodology allows to obtain high resolution structures of complex biomolecules and molecular machines such as chromatin, supercoiled DNA, intracellular vesicles, ion channels and single viral particles. In this course, fundamentals of X-ray diffraction and modern methodologies, including time resolved, neutron, X-ray free-electron laser and ultrahigh resolution crystallography will be illustrated, together with the theoretical bases of electron microscopy and some interesting applications. A number of interesting recent applications, including those that have allowed to delineate the mode of action of Pt-, Ru- and Au-based drugs will be presented. In this respect, crystallographic studies on the interaction between metal-based drugs, like cisplatin, carboplatin and oxaliplatin, and both DNA and proteins will be discussed. Recent structural studies that reveal the molecular bases of protein-gold compounds and protein-ruthenium compounds recognition will be also analyzed. |
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Final evaluation |
The assessment will be done by illustration and discussion of a recent paper concerning the topics of the course. |