2.7.2 Molecular Docking

Molecular docking computationally predicts the preferred orientation (or 'pose') of a small molecule within the binding site of a target protein, and...

Molecular docking computationally predicts the preferred orientation (or 'pose') of a small molecule within the binding site of a target protein, and estimates the strength of that interaction using a scoring function that accounts for hydrogen bonding, hydrophobic contact, electrostatic complementarity, and steric fit. Docking proceeds in two conceptually distinct steps: a search algorithm generates a large number of candidate poses for each ligand within the defined binding site, and a scoring function then ranks these poses (and, across compounds, ranks different ligands against one another) by predicted binding affinity. Widely used docking platforms include AutoDock Vina (freely available), Glide (part of the Schrödinger Maestro suite), and GOLD. Because scoring functions remain imperfect approximations of true binding thermodynamics, docking results are conventionally treated as a hypothesis-generating filter rather than a definitive prediction, and top-ranked compounds are always confirmed experimentally using the receptor-binding and functional assays described in Phase 3.