QM study on inhibition mechanism of human carbonic anhydrase (II) enzyme by Boric acid derivatives inhibitors: Kinetic and thermodynamic investigation

QM study on inhibition mechanism of human carbonic anhydrase (II) enzyme by Boric acid derivatives inhibitors: Kinetic and thermodynamic investigation

In this research, the electronic structure and inhibition mechanism of some boric acid derivatives as new inhibitors for the inhibition of human α -carbonic anhydrase (ΙΙ) enzyme, α-hCA(ΙΙ), have been investigated using quantum mechanical calculations. At the first step, selective inhibitors and enzyme model were optimized using B3LYP/6-311+G** method in two gas and lipoprotein solvent phase, and then the interaction between enzyme and inhibitors was investigated. The used enzyme model in this research including the zinc ion (Zn2+) in the catalytic center of enzyme active site with four coordination number which 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 the results of scanning calculations, a square-shaped transition state is formed and then by passing through an intermediate 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) boronic acid 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.