24721 - Innovative Computer-Based Methodologies in Drug Design

Learning outcomes

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

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.

Readings/Bibliography

• H.D. Hoeltje e G. Folkers, Molecular Modeling, Basic principles and applications, VHC, Second Edition 2003
• A.R. Leach, Molecular Modelling, Principles and Applications, Person Education Limited, 2001

Teaching methods

Lessons 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

Computer room

Office hours

See the website of Andrea Cavalli