Enrichment of potent GSK-3β inhibitors from docking studies in the enzyme active site

We have presented molecular docking studies using Glide, in the active sites of the X-ray crystal structures and induced fit models of glycogen synthase kinase-3β (GSK-3β). Using the docking score as the ranking metric, we have computed the enrichment of known GSK-3β inhibitors which are seeded in a decoy set of World Drug Index compounds. Interestingly, our studies have found that extra precision docking of compounds into the ensemble of protein structures either from X-ray data or induced fit models and ranking them by GlideScore, lead to the best retrieval of actives in the top 5% and 10% of the database with significant enrichment. Our studies emphasize the significance of induced fit models in such enrichment when experimental data are limited.