Virtual screening experiments were performed using the Surflex docking program [7, 53, 54] with an empirical scoring function (based on the Hammerhead docking system). The empirical scoring function has been updated and re-parameterized with additional negative training data along with a search engine that relies on a surface-based molecular similarity method. Standard parameters were used as implemented in the SYBYL software (version 8.1) [51]. The search strategy of Surflex employs an idealized ligand (called protomol), which utilizes various molecular fragments. Molecular fragments were tessellated in the active site and optimized based on the scoring function. The search algorithm utilized the morphological similarity function, which is evaluated between the protomol and the putative ligands. For the docking algorithms, a post-dock minimization procedure was applied using the BFGS quasi-Newton method and an internal Dreiding force field. For each compound, the top 30 ranked poses were saved.