Biochemistry applied to the rational design of biologically active molecules

A.Y. 2015/2016
5
Max ECTS
48
Overall hours
SSD
BIO/10
Language
English
Learning objectives
This course mainly aims to provide (i) the theoretical bases for the understanding of drug development approaches exploiting structural and functional information on the target proteins and (ii) the tools for designing and testing of putative biologically active molecules. Thus, the course is ideally linked to that on "Advanced chemical methods in biotechnology", especially part 2, while some aspects of structural biology will be further expanded in the "Structural Proteomics" elective class.
Part 1 (Structural biology) will focus on protein structures and techniques for structure-based drug design and screening, while part 2 (Enzymology) will present the tools of mechanistic enzymology used for testing and designing biologically active molecules.
As an added value, this class will provide knowledge and tools to study structure-function relations of proteins, which are needed to elucidate biological processes, for protein engineering and all sound biotechnological applications of proteins.
Expected learning outcomes
Undefined
Course syllabus and organization

Single session

Lesson period
Second semester
Course syllabus
Structural Biology (2 CFU)
- Introduction to the identification of drug molecular targets by bioinformatic, genomic, transcriptomic, and proteomic techniques. Criteria for the validation of pharmacological targets.
- Techniques and strategies for the overexpression and purification of molecular targets, especially proteins and enzymes.
- Review of information on the covalent structure of proteins, their three-dimensional architectures and the factors that stabilize their native conformation. Protein modules and classification of globular proteins. Subunit-subunit interactions. Structure-sequence correlation: homology modelling. Protein stability and flexibility.
- Molecular recognition, localization and nature of ligand binding sites. Structure-function relationships for enzymes: active site geometry, proximity factor and destabilization of the fundamental state, stabilization of the transition state and water exclusion. Strategies for the identification of catalytic residues and of interaction sites with ligands and effectors (docking techniques). Structural basis of enzyme inhibition. Examples.

Enzymology (3 CFU)
- Principles of chemical and enzyme catalysis.
- Design of robust enzyme activity assays for the dissection of enzyme kinetic mechanisms and testing of putative effectors (activators/inhibitors).
- Kinetic approaches to dissect enzyme chemical and catalytic mechanisms
- Classes of active site inhibitors and inactivators and kinetic methods to determine inhibition mechanisms and inhibitors' potency.
Concepts and their applications will be illustrated with examples taken from the literature.
BIO/10 - BIOCHEMISTRY - University credits: 5
Practicals: 16 hours
Lessons: 32 hours
Professor(s)
Reception:
Thursday, 10:30-12:30
Dept. of Biosciences, C tower, 5th floor
Reception:
Monday, 1 pm -2 pm
Protein Biochemistry Unit, DSBB, Via Celoria 26, 5C