LIGAND LIBRARY

Figure 1: The 4 catalogs used from ZINC Databases.





1,677,767 molecules to screen

The ZINC Databases (ZINC12 & ZINC15) provide structures of commercially-available compounds for virtual screening [ref 1-2].

Four catalogs from ZINC were used to target the HIV-1 capsid protein :

  • HMDB (Human Metabolole Database) → small molecule metabolites found in the human body;
  • FDA → approved drugs;
  • ChemBridge → chemicals distributor;
  • MayBridge → chemicals distributor.
  • A total of 1,677,767 molecules are used, providing a wide range of structures which differ in number of atoms, H-bond acceptors/donors, torsion angles, and forks. (see STATISTICS below)

    References

    1. John J. Irwin, Teague Sterling, Michael M. Mysinger, Erin S. Bolstad, and Ryan G. Coleman. ZINC: A Free Tool to Discover Chemistry for Biology. Journal of Chemical Information and Modeling 2012 52 (7), 1757-1768. DOI: 10.1021/ci3001277
    2. Teague Sterling and John J. Irwin. ZINC 15 – Ligand Discovery for Everyone. Journal of Chemical Information and Modeling 2015 55 (11), 2324-2337. DOI: 10.1021/acs.jcim.5b00559


    STATISTICS





    Ligand Diversity

    You can hover your mouse cursor over the graphs, and clik on their legend to see more details.

    The ~1.6 million ligand structures differ in size, in their physico-chemical properties, and their conformational space.

    ~60% of the ligand structures are composed of 23 to 29 heavy atoms (different than Hydrogen atoms). The smaller ligands contain 4 heavy atoms, and the larger ones 44.

    Different physico-chemical properties could be deduced from the ligand structures. They contain specific atoms and substructures which could interact with the capsid protein. Such as :

  • atoms O, N, S involved in H-bond interactions (as acceptor or donor);
  • aromatic rings which could form π-π, Cation-π, and OH-π interactions;
  • aliphatic chains which could take place in hydrophobic pockets.
  • Finally the intrinsec flexibility of the ligands is also a criteria of diversity. This property is directly linked to the conformational space the docking sofware have to explore in order to found the right pose in the capsid structure. It depends on the number of forks (roots of several branches) and the number of torsion angles (connexion between 2 atoms that can be used as a rotation axis) in the ligand structure.

    EXAMPLES


    Below are presented 3 different ligands, which differ in number of heavy atom, H-bond acceptor/donor, torsion angle, and fork.

    You can hover your mouse cursor over the graph, and clik on the legend to see more details.