Simulation Modeling of Biomolecules

Goals
The course aims to provide students with the principal techniques used in the modeling of biological macromolecules. Both the general principles of the most important approaches and their applications to biologically and pharmaceutically relevant systems, such as enzymes, receptors, polypeptides, protein-protein and ligand-protein complexes, will be discussed.

Course content
Basic concepts:
- Basic molecular modeling. Force fields.
- Statistical mechanics review.
- Molecular dynamics.
- Monte Carlo method.
- The sampling problem. Enhanced sampling methods. Parallel tempering.
- Free energy calculation. Thermodynamic perturbation and integration.
- Umbrella sampling. Jarzynski equality based methods.
- Simplified approaches to calculate binding free energies (MM/GBSA, MM/PBSA).
- Analysis of data from molecular simulations. Essential Dynamics. Communication propensity.

Applications:
- Force field-based conformational analysis.
- Approaches to obtain 3D models of medium size, flexible molecules.
- Computer-aided drug design.
- Molecular docking.
- Protein-protein interactions: how to model them?
- Design of modulators of protein-protein interactions.
- The problem of protein folding. Folding inhibitors drugs.

Reference material
- M.P. Allen, D.J. Tildesley, Computer simulation of liquids.
- A. R. Leach, Molecular Modelling - Principles and Applications, Longman
- Suggested research papers on specific subjects.

Prerequisites
Basic knowledge of math, physics, physical and organic chemistry

Assessment method
Oral exam. The exam will consist of a discussion which aims to verify the preparation of the student on the course contents. The examination will typically include a few questions concerning both basic simulation methods and their applications to the study of biomolecules.

Language of instruction: english

Attendance Policy: highly recommended

Mode of teaching: traditional