Screening allows for reducing the compounds which need to go to experimental testing. Our docking protocol, where we used KDEEP to re-score docked poses, won 2 blind sub-challenges of the D3R Grand Challenge 4. With our docking software, we can cover several relevant scenarios:
- Free docking: No restrictions or prior knowledge is imposed in the docking exercise. Poses are re-scored with KDEEP.
- Scaffold-hopping: Identify compounds in your library with great pharmacophoric overlap against a known binder.
- Ensemble docking: We build an ensemble of conformations for your pocket to model protein flexibility.
- Template docking: Use a known binder to guide the docking of a similar compound or series.
- Constrained docking: Impose restrictions so certain moieties in the ligand (e.g. aromatic rings) are placed in the right spot.
- Protein preparation: The most suitable protonation states will be determined and hydrogens will be added.
- Mixed solvent molecular dynamics: The protonated target is simulated in a mixture of water and a fragment-size molecule, like benzene.
- Pocket profiling: Pharmacophores, structural waters and pocket ensembles are obtained from the simulations.
- Homolog search: Exhaustive search among public databases to find similar homologs with bound small molecules to further refine the pharmacophore.
- Molecular docking: The library of choice will be docked against the pocket ensemble and the obtained poses will be rescored after taking the pharmacophore and the waters into account.
- Ranking: The best compounds will be inspected and a short list of the most promising ones will be provided.
- A PlayMolecule scene with binding mode predictions for the most promising compounds.
- A ranking of compounds.
- An extensive report summarizing the structural insights obtained.