Theozymes are theoretical catalysts, constructed by computing the optimal geometry for transition state stabilization by model functional groups. They may be used to quantitate the relative stabilization of reactants and transition states by biological and non-biological catalysts. Theozymes have been used to address many interesting problems in catalysis.
The following picture shows a typical theozyme bound to transition states relevant to peptide hydrolysis by HIV protease. This theozyme (along with many others that have been used to elucidate the mechanisms of various biological catalysts) is discussed in the Current Opinion in Chemical Biology review listed below.
In this next picture, the crystallographically-determined array of functional groups around an ammonium-N-oxide hapten in a catalytic antibody active site is compared to a theozyme predicted to bind tightly to this hapten and the transition states it mimics. This prediction was made years before any structural information was known, yet the congruence between the predicted and observed structures is striking! This demonstration of the potential of theozymes for catalyst design is described in detail in the book chapter listed below.
This final picture shows the computed structures of a bis-ammonium theozyme complexed to the reactant and transition state for the decarboxylation of a carboxybenzisoxazole. This recent application of the theozyme technique is described in the third paper listed below.