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.
During the course, the first principles (forces, interactions and processes) that are the basis of non-covalent chemistry will be presented. With a look at natural systems, the course leads the students to understanding self-assembly phenomena and enable them to design supramolecular devices. To this end, an overview of material-related applications will be presented
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.
This course mainly consists of class lectures plus one or two laboratory sessions.
Molecular representation (graphs, fingerprints, MIF) and
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.
Introduction to supramolecular chemistry: the fundamentals of non-covalent synthesis
Nature as a Model: learning as to read molecular and supramolecular information (DNA, proteins). Relationships between structures (primary, secondary, tertiary) and function. Allosteric effect. Hierarchy of self-assembling and kinetic inertia: thermodynamics and kinetics at work
-Nature of non-covalent interactions. The role of solvent: solubility and solvofobicity.
-Classification of synthetic supramolecular compounds. Chelation effect and macrocycle effect. Organization and complementarity.
Non-covalent synthesis and covalent synthesis: a marriage of convenience
-Anion Receptors. Cation Receptors. Neutral molecule receptors.
- Supramolecular architectures, ideas of crystal engineering.
- Supramolecular stereochemistry. Intrinsic chirality and induced chirality. Chiral memory.
-Catalysis and supramolecular reactivity. Self-replication.
Supramolecular at Work: Nanotechnologies.
-Imaging (MRI, luminescent probes, radiolabeling), radiotherapeutic compounds
- Selective ionic electrodes (ISEs), iono-selective membranes, chromo ionophore, piezoelectric and fluorescence sensors, electronic nose
- Optical and hybrid switches.
-Logic gates (YES, NOT, AND, OR, XOR) from supramolecular systems.
Future Applications: nanomacchine
- Top-down and bottom-up strategies for building nanostructures.
- Molecular machines in the biological world. Artificial molecular machines.
handouts provided by the teacher
Notes from classes