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 the class, the students will be able to:
1. illustrate the basic concepts of equilibrium thermodynamics including internal energy, en-thalpy, entropy, and Gibbs free energy;
2. create suitable mathematical models for an accurate description of the covalent and non-covalent interactions involved in biological phenomena such as protein folding, allostery, and substrate binding;
3. describe the main characteristics of Force Fields employed in computer simulations of bio-molecular systems;
4. illustrate the workflow and main applications of popular computational chemistry tech-niques, i.e. molecular dynamics and Monte Carlo sampling;
5. link the computational study, performed at the microscopic molecular level, of biological phenomena like protein folding to their macroscopic thermodynamical investigation;
6. 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 or-ganic molecules; and
7. have learnt about chemical probes for mechanism of action studies in vitro and in vivo (pho-toaffinity ligands, biotin conjugates, etc.); and about their use in target validation studies (affinity chromatography, photoactivation, etc.).