Quntum mechanical study On interaction between Carbonic Anhydrase Bio Catalyst Model Enzyme with New Class Of Inhibitors

Carbonic anhydrases (CAs) are a superfamily of metallo-enzymes, which catalyzed the reversible and simple reaction of carbon dioxide hydration to bicarbonate and proton, eq ۱.CO۲ + H۲O HCO۳- + H+ (۱)There are five genetically distinct groups of carbonic anhydrase enzymes known as α, β, γ, δ and ζ [۱-۳]. α-CA as the first and the most important group of the carbonic anhydrase family, has been found in vertebrates, monocytes, algae, and finally in the cytoplasm of green plants and in some bacteria. In the present research a new class inhibitors of different carbonic anhydrase (CA) isoforms are investigated using DFT calculations. The most advantage of DFT method is a significant increase in computational accuracy without the additional increase in computing time.۲The harmonic vibrational frequencies were calculated to confirm that a full optimized structure correctly corresponds to a local minimum which has only real frequencies. In addition, the vibrational frequencies have been employed to obtain enthalpies and Gibbs free energies at ۲۹۸.۱۵ K and ۱.۰ atmosphere pressure. All calculated enthalpies were zero-point (ZPE) corrected with unscaled frequencies. Our results indicate that these kind of inhibitors, inhibited the human carbonic anhydrase with very different inhibition profiles compared to other inhibitors. According to calculated results, studied inhibitors are anchored to the non-protein zinc ligand (hydroxyl ion) by means of a hydrogen bond and an intermediate complex is formed, [(his)۳Zn(II)(OH)/inhibitor], which is in good agreement with experimental data. In continue the active form of the CA enzyme converted to inactive form. Finally, the HOMO-LUMO and AIM analysis have been done to understand the details of interaction between studied inhibitors and CA active center in intermediate complex in solvent phase.