qm study on inhibition mechanism of human carbonic anhydrase (ii) enzymeby boric acid derivatives inhibitors: kinetic and thermodynamic investigation

In this research, the electronic structure and inhibition mechanism of some boric acid derivatives as newinhibitors for the inhibition of human α -carbonic anhydrase (ιι) enzyme, α-hca(ιι), have been investigatedusing quantum mechanical calculations. at the first step, selective inhibitors and enzyme model wereoptimized using b3lyp/6-311+g** method in two gas and lipoprotein solvent phase, and then theinteraction between enzyme and inhibitors was investigated. the used enzyme model in this researchincluding the zinc ion (zn2+) in the catalytic center of enzyme active site with four coordination numberwhich is connected to three histidine amino acids and one hydroxyl ion in the active form of the enzyme.scan calculation was used to find the best interaction distance between enzyme and inhibitor. based on theresults of scanning calculations, a square-shaped transition state is formed and then by passing through anintermediate the reaction product is formed. finally, the results of calculations show that [1,1-biphenyl]-4-yl boronic acid molecule with the smallest energy barrier (54.68 kcal/mol ) and (e)-(4-methylstyryl) boronicacid with the highest energy barrier (62.14 kcal/mol), are predicted as the strongest and weakest inhibitors,which is in good agreement with the experimental results.