90823 - Biomolecular Simulations for Drug Design

Course Unit Page


This teaching activity contributes to the achievement of the Sustainable Development Goals of the UN 2030 Agenda.

Good health and well-being

Academic Year 2021/2022

Learning outcomes

At the end of the course, the student knows the theoretical and practical aspects related to molecular simulations of pharmaceutically relevant biological systems. In particular, the student knows the basics of several computational methods (including docking and Molecular Dynamics), and how to integrate them for designing or selecting bioactive compounds. Finally, the student is able to plan and setup virtual experiments and run calculations with widespread open-source software for biomolecular simulations.

Course contents

Module 1 (3 CFU: 24 hours, frontal lectures)

- Introduction and basic concepts
The drug action process: pharmaceutics, pharmacokinetics, pharmacodynamics.
The molecular targets of drug action: definition and examples; thermodynamic representation of the drug-target interaction.
Drug-target interactions: covalent and non-covalent, enthalpic and entropic.

- The drug discovery paradigm
The "magic bullet"; examples: penicillins, steroid hormones derivatives, kinase inhibitors.
Polypharmacology and multi-target drugs.
Targeting pathways and systems.

- In silico drug design strategies
Target-based approaches: virtual screening; FBDD (fragment-based drug design).
Ligand-based approaches: pharmacophores and database searching; QSAR and chemoinformatics.
Network-based approaches.

- Presentation of case studies

Module 2 (1 CFU: 8 hours, frontal lectures; 2 CFU: 30 hours, laboratory)

Static modeling (theory). Potential energy functions for molecular modeling. Minimization algorithms. Conformational analysis: grid search and genetic algorithms. Basic principles of Monte Carlo simulations. Practical aspects of protein-ligand docking.

Static modeling (laboratory). Drawing and building of small molecules. Crystallographic structures of proteins for target-based drug design (Protein Data Bank). Setting up and running a molecular docking simulation.

Dynamic simulations (theory). Basic principles of Molecular Dynamics simulations. Simulation of experimental/physiological conditions for complex biological systems (water-soluble proteins, membrane-embedded proteins, nucleic acids, …).

Dynamic simulations (laboratory). Setting up and running a Molecular Dynamics simulation.


Reading material provided by the teachers during the lectures.

A.R. Leach, Molecular Modelling: Principles and Applications, Person Education Limited, 2nd edition, 2001.

Teaching methods

Frontal lectures and training exercises on the computer with the support of tutors.

Assessment methods

Module 1: students will be required to present and discuss orally a written short (3-5 pages) summary of a research paper retrieved from the literature reporting a work dealing with an argument inherent to the course program (computational design/identification of bioactive compounds). During the discussion, further questions inherent to the program will be asked.

Module 2: students will be evaluated based on the achievement of tasks assigned during the laboratory.

The modules will be evaluated separately and the final score will be calculated as the average of the scores of the single modules.

Teaching tools

Electronic slides, scientific papers, and other teaching materials available through the Virtuale platform.

Office hours

See the website of Maurizio Recanatini

See the website of Matteo Masetti