Computational docking provides a means to predict and assess interactions between ligands and proteins with relatively little investment. Application to proteins involved in disease holds the promise of discovering new drug therapeutics. After decades of method development and application, this promise has not been fully realized. The CANDOCK algorithm confronts several outstanding technical and practical problems in computational docking. One significant problem is assessing goodness-of-fit, or the likelihood that the given pose is the most physically realistic (native-like) pose among many unrealistic binding poses. Another significant limitation is the lack of full protein flexibility in the docking methods used today. The induced fit is a widely recognized challenge in computational drug screening, where the protein and the ligand undergo conformational changes upon ligand binding.