Catalytic role of proton transfers in the formation of a tetrahedral adduct in a serine carboxyl peptidase

Quantum mechanical/molecular mechanical MD and 2D free energy simulations are performed to study the catalytic role of proton transfers in the formation of a tetrahedral adduct in a serine carboxyl peptidase. It is shown that the proton transfer process in these enzymes are likely to be more complex as both general base and acid catalysts are required for the formation and stabilization of the tetrahedral adduct.