Program :
This course is designed to provide hands-on learning of in silico preparation of chemical libraries for virtual screening based on the structure of reference ligands and to perform ligand-based virtual screening. The program includes parts
- Mastery of the different molecule file formats and handling of PDB, smile, SMARTS, mol2, MDL-sdf, 3D molecules with Pymol, Advantages, limitations and frameworks of use of different file types.
- Generation of three-dimensional molecular models for small molecules (1D/2D to 3D) and calculations of ligand descriptors and transformation from 2D to 3D format and dimensions using software ( knime rdkit, frog and openbabel) (different behaviors: Smart change, isomer, tautomer).
- Descriptors visualization, molecules visualization
- Pharmacophores & main ADME/tox rules : Lipinski, Weber, Egan,...
Notion of Frequent, Hitter, Aggregants, Toxic Fragments using FAFdrug
- Ligand-based screening, (notion of decoys)

Objectives in terms of knowledge :
Practical learning of in silico preparation of chemical libraries for virtual screening, based on the structure of reference ligands including a part i) generation of three-dimensional molecular models for small molecules (1D/2D to 3D), how to go from 1D-2D-3D ii) calculation of ligand descriptors, iii) pharmacokinetic aspects (ADME/tox) based on specific physicochemical criteria, iv) application of a ligand-based screening.
Targeted skills :
Generation of compound libraries and ligand-based screening.