QM study on the mechanism of Carbonic anhydrase II inhibition with glycosylcoumarin as non-zinc mediated inhibitors from thermodynamic view point

Carbonic anhydrase (CA) is an enzyme having zinc metal that catalyzes the reversible reaction of conversion of carbon dioxide to Bicarbonate. In this research the mechanism of inhibition a new class of inhibitor of this enzyme, glycosyl coumarin has been modeled using the density functional theory (DFT). First, the most constant confirmer of this four coumarin sugar derivatives which includes galactose, mannose, ribose and glucose has been selected and then they had been interacted as inhibitor with CA (II) enzyme’s active site. In further for showing the effect of sugar in these molecules, coumarin itself had been chosen as inhibitor and the inhibitory effect is surveyed. All calculations have been done by density functional theory (DFT) in level of B3LYP with basic set 6-31G* and with Minnesota function M06 with basic set 6-31+G*. Thermodynamic functions like enthalpy of formation, entropy of formation and Gibbs free energy for CA-inhibitor have been computed. The computed thermodynamic functions show that although this coumarin sugar derives have deterrence in the range of micro molar but, coumarin without sugar is a stronger deterrence for CA II.

Keywords:

Carbonic Anhydrase , glycosylcoumarin , Density functional theory