MOLECULAR DESIGN AND STRUCTURE PROPERTY RELATIONSHIPS

The course will show the relevance of chemioinformatics in chemical research. Although chemioinformatics methods are mainly applied in the chemical-pharmaceutical field, the student will be sensitized to the possibility of applying such methodologies to various fields of chemistry.
The course should allow the student to acquire the following basic knowledge:
Know the definition of chemioinformatics and its historical evolution;
Understand the importance of chemioinformatics in various chemical research fields, with particular attention to drug discovery procedures.
Know the economic aspects of chemioinformatics, which allows to reduce the cost of the survey.
Know the basics of chemioinformatics.
Know the basics of drug metabolism and the methods associated with that research field.
Know chemioinformatics methodologies to be applied to the study of drug human metabolism.

This course aims at providing the concepts for the application of the physical organic chemistry to drug discovery. In particular, the main physical chemical and ADME properties of drugs or potential drugs will be discussed, to learn how to modulate them through the modulation of their chemical structure.

Main knowledge acquired will be:

1) Basic concepts of the drug discovery and drug development processes

2) Knowledge of the main aspects of absorption, distribution, metabolism, excretion and toxicity (ADMET) of drugs

3) Knowledge of experimental and in silico methods for the determination of acid-base properties, lipophilicity, permeability and solubility

4) Knowledge of the main chemical strategies for ADME optimization

5) Knowledge of methods for structure-activity relationship studies

Understand the basic principles of designing drugs and classical methods associated with this field of research.
Know chemioinformatics methodologies to be applied to drug design.

The teaching will take place through the discussion of the various topics reported in the program and will include days dedicated to the clarification of doubts and the simulation of the oral exam.

Chemometrics concepts
Molecular representation (graphs, fingerprints, MIF) and
molecular minimitation.
Advanced molecular descriptors. QSAR and 3D-QSAR.
Circular molecular descriptors: the Moka method.
3D molecular descriptors: the VolSurf method.
Applications of the VolSurf method in the field of ADME
Calculation methods of bitstrings and fingerprints. Methods of calculating molecular similarity.
The Flap method for the calculation of molecular similarity.
The Flap method for the calculation of affinity with macromolecules.
Computational methods for metabolism prediction. The MetaSite method.

Computer exercises

handouts provided by the teacher