Despite the limited access to conformationally diverse and high-resolution structures of human P-gp when our docking studies were performed, the work presented here shows a two-fold increase (13.4%) in hit rate for compounds that reverse multidrug resistance in P-gp-overexpressing cancer cells, thereby validating the use of our P-gp model to virtually screen small molecules with molecular docking, and the use of counter-selective docking to target the NBDs. The gene discussed is PGP; the disease is cancer.