While the hydrolytic products of OP breakdown by OPH are generally of reduced toxicity relative to their parent compounds , catalytic rates (k cat ) and substrate binding constants (K M ) are inadequate for therapy. Many traditional protein engineering studies have shown that inducing mutations in or near the active site residues can increase the substrate specificity (k cat /K M ) by increasing the catalytic activity of the enzyme . Those efforts, however, resulted in OPH variants with reduced effectiveness for hydrolysis of multiple nerve agents. In particular, the wild-type OPH and variants currently available demonstrate poor substrate binding affinity (K M ). Poor binding affinity means that the substrate concentration required for enzymatic conversion exceeds the nerve agent lethal dose. Therefore, an important topic of research is understanding how the structure of OPH correlates with substrate binding.