Docking to multiple pockets or ligand fields for screening, activity prediction and scaffold hopping

Two recent technological advances dramatically reducing the rate of false-negatives in activity prediction by docking flexible 3D models of compounds include multi-conformational docking (mPockDock) and the docking of candidates to atomic property fields derived by co-crystallized ligands (mApfDock).

The mApfDock and mPockDock provide the AUC of 90.4 and 83.8%, respectively. The mApfDock gave better performance when compounds required large induced-fit pocket changes unseen in crystallography, whereas the mPockDock is superior when the co-crystallized ligands do not represent sufficient chemical and binding location diversity.

Both approaches proved to be efficient for scaffold hopping; they are complementary when the coverage of the co-crystallized complexes is poor but become convergent when the complexes are diverse enough.