Course Unit Page

Academic Year 2018/2019

Learning outcomes

Analytical methodologies in medicinal chemistry

The course is aimed to provide an overview focused on the role played by analytical methodologies in drug discovery and development. The course should allow learning about the molecular recognition mechanisms, by making use of analytical techniques (circular dichroism, SPR based optical biosensor, mass spectrometry, affinity chromatography). At the end of the course the student is able to determine the binding parameters of the drug/protein complex and to evaluate the role of the different analytical techniques in the characterization of the molecular recognition mechanisms.

Computational methods in medicinal chemistry

The theoretical course is aimed at providing the knowledge related to computational approaches to drug design. In details, the approaches based on ligand (ligand-based) and target (structure-based) will be introduced and some successful examples reported.

The computational medicinal chemistry laboratory is aimed at providing the knowledge about some molecular modeling software currently used at academic and industrial level during the drug design phase of a drug discovery project.

Course contents

Analytical methodologies in medicinal chemistry

1. High Performance Affinity Liquid Chromatography (HPALC): immobilization of receptors, enzymes and plasma proteins; screening of new compounds for their affinity to the target and their activity; binding parameters and displacement chromatography; reversible and covalent modification of the protein.
2. Polarized light spectroscopy: secondary structure of proteins; biomolecular recognition mechanism; functional conformational transitions; determination of binding parameters; stereochemical characterization of the target bound drug.
3. Label free surface plasmon resonance (SPR) based optical biosensors: principle of SPR and instrumentation; recognition processes, fishing for new targets; screening of new compounds for their affinity to the target protein; kinetics of the molecular recognition process.
4. Hyphenated techniques (HPALC/MS/MS, SPR/MS/MS): specific applications to ligand fishing, post-translational modifications, screening of enzyme inhibitors, modulation of protein/protein interactions.

Lectures will be followed by laboratory practice on the structural characterization of the drug/protein complex and on the use of optical biosensor and cicular dichroism to study the biomolecular recognition mechanism (drug/protein and protein/protein).

Computational methods in medicinal chemistry

The course will be composed by theoretical lessons and computer-based laboratory exercises.

1) Drug design and discovery

- Drug discovery: the classical paradigm in the post-genomic era (serendipity; screening; chemical modification; rational design)

- Rational drug design (introduction and basic concepts; pharmacophore-based drug design; target-based drug design; integrated approaches)

2) Molecular modeling

- Molecular geometry

- Molecular energies (force field; ab initio quantum chemical methods)

- Conformational analysis (Monte Carlo; molecular dynamics)

- Advanced sampling methods (metadynamics; parallel tempering)

3) Pharmacophore-based drug design

- Analysis (data collection; pharmacophore construction)

- Design methods

- Examples

4) Target-based drug design

- Analysis (ligand-target interactions; docking simulation; virtual screening)

- Design methods

- Examples

5) Laboratory of computational medicinal chemistry

- Construction of ligands

- Example of conformational analysis

- Analysis of 3D protein structures and ligand-target complexes

- Docking simulations

- Internet DataBank: PDB, ExPASy, PubMed, Etc.

- Molecular modeling software: ISIS Draw, RasMol, VMD, PyMol, etc.


1. V. Cavrini, V. Andrisano. Principi Analisi farmaceutica. Società editrice Esculapio ed. 2013.

2. Lecture slides and specific articles and reviews

3. H.D. Hoeltje e G. Folkers, Molecular Modeling, Basic principles and applications, VHC, Second Edition 2003

4. A.R. Leach, Molecular Modelling, Principles and Applications, Person Education Limited, 2001

Teaching methods

Lessons, advanced analytical methodologies lab and computer-based exercises

Assessment methods

An interview for the theoretical part and a detailed description of the interactions of a ligand-protein complex of pharmaceutical interest, for the computer-based laboratory.

Teaching tools

PowerPoint slides and papers

Laboratory of advanced analytical methodologies

Computer room

Office hours

See the website of Manuela Bartolini

See the website of Matteo Masetti