The selective hydrolysis of the extremely stable peptide or amide bond of peptides by small molecule mimics of metalloenzymes is required in a wide range of biological, biotechnological and industrial applications. We have employed innovative theoretical techniques including molecular dynamic simulations, quantum mechanics and quantum mechanics/molecular mechanics to elucidate the mechanisms of mono- and binuclear metal center containing enzymes (insulin degrading enzyme (IDE) and leucine aminopeptidase (LeuAP) respectively) and their existing synthetic analogues. In the first step, we have investigated the roles of metal ions, ligands, second coordination shell residues and the protein environment in the catalytic functioning of IDE and LeuAP. In the next step, the knowledge of the roles of metal ions and the ligand environment in the mechanisms of existing synthetic analogues (e.g. Pd(II), Cu(II) and Zr(IV) metal complexes) of enzymes is combined with the information acquired in the first step to design more efficient catalysts.

Theoretical development of bio-inspired catalysts for efficient peptide hydrolysis

245th National Meeting (2013)

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