Spectroscopic and molecular modeling studies on binding of dorzolamide to bovine and human carbonic anhydrase II.

This report is a comparative evaluation on the interaction of dorzolamide (DZA) with bovine and human carbonic anhydrase II (bCA II and hCA II, respectively) using fluorimetry, UV-vis and circular dichroism (CD) spectroscopy as well as molecular docking and molecular dynamics studies. Fluorescence data obtained at different temperatures indicated that DZA quenched the intrinsic fluorescence of both enzymes through a static mechanism. Thermodynamic analysis of the quenching data revealed that hydrogen bonding and van der Waals interactions play important roles in drug binding. Calculations of the protein surface hydrophobicity (PSH) index, using 1-anilinonaphtalene-8-sulfonate, also indicated a decrease in PSH of the hCA II and minor increase in PSH value of the bCA II upon drug binding. The results of far- and near-UV CD experiments showed some alterations in the secondary and tertiary structures of both enzymes upon ligation. The structural changes induced by drug binding caused more reduction in the catalytic activity of hCA II than bCA II. Based on the experimental data and the possible binding mode revealed by molecular docking and molecular dynamic studies, we concluded that DZA binds stronger to hCA II active site cavity compared to bCA II.