| Enzymes are created by nature to be efficient biological catalysts. Enzymatic kinetics and protein-substrate interactions were surveyed. Various enzymatic mechanisms ranging were summarized.; Hybrid density functional theory calculations were used to calculate the activation barriers of nitrile oxide cycloadditions to the unsymmetrical alkynes cyanoacetylene and methyl propiolate. Inherent electronic effects and solvent polarity both influence regioselectivity.; An antibody (29G12) elicited against an achiral hapten was found to catalyze the formation of one single regio- and enantioselective 1,3-dipolar cycloaddition adduct (5R-acylisoxazoline). Quantum mechanical calculations predict that the 5-substituted transition state is favored over the 4-substituted transition state, and the antibody stabilizes the lower-polarity transition state relative to the ground state.; Computational studies of 29G12 ranging from quantum mechanics, molecular docking and molecular dynamics showed that all the transition states bind into the crystal structure differently from the hapten. The 5R transition state has one hydrogen bond with Lys 202 and one backbone hydrogen bond with Glu 204. The predicted 5R transition state binding energy was in good agreement with experiment.; A diradical intermediate of ketone photolysis from the Norrish type II photoreaction only gives cleavage products: a ketone and an alkene. The same reaction catalyzed by antibody 20F10 generates more cyclization products than cleavage with high enantioselectivity. Quantum mechanical calculations suggested that both cyclization and cleavage are under entropy control. Hapten, substrate and transition state docking studies showed that the cis-hapten, substrate and the cyclization transition state have similar binding modes. Tyr L36 and His L91 can act as sensitizers for the cyclization process.; Quantum mechanical calculations were carried out for reactions of benzisoxazole with acetate and butylamine as general bases in water and acetonitrile using continuum solvent models. Docking studies indicates that Glu H50 can act as a general base in an otherwise hydrophobic binding pocket. Albumins can employ Lys 199 in one of its binding sub-domains (IIA) to catalyze elimination. Microenvironments made up of catalytic polar groups (glutamate in 34E4 and lysine in human serum albumin) surrounded by relatively nonpolar groups are present in both catalytic proteins. |
