Structural Chemistry

This course is intended to provide the student with a theoretical, analytical and applied background in the fields of rational drug design and of target-oriented chemical optimization of bioactive compounds. In particular, modern chemical-physics methods for the investigation of the molecular target-ligand interaction will be discussed in the context of the expanded role of chemistry through the process of the design and optimization of pharmacologically active molecules; and modern, chemistry-directed approaches to assist the identification of novel molecular targets (chemical tools and probes, chemical genetics) will be described.
The course is ideally linked to those dealing with structural biology, bioinformatics, nanotechnologies, protein engineering and molecular enzymology.

At the end of this class, the students are expected to:
(1) have refreshed basic concepts in thermodynamics;
(2) have learnt the physics behind non-covalent interactions, and how to model them;
(3) have acquired the basics of molecular mechanics and molecular dynamics, with emphasis on how to use this knowledge to model complex structures and time-dependent phenomena (structure fluctuations, allostery and molecular docking);
(4) have acquired basic concepts in crystallography, to profitably read the related scientific literature;
(5) have understood how computational methods (structure-based, ligand-based and fragment-based drug discovery) support the fast, effective design and optimization of biologically active, small organic molecules; and
(6) have learnt about chemical probes for mechanism of action studies in vitro and in vivo (photoaffinity ligands, biotin conjugates, etc.); and about their use in target validation studies (affinity chromatography, photoactivation, etc.).