Complexation of nanoscale enzyme inhibitor with carbonic anhydrase active center: A quantum mechanical approach

Abstract

The complex between carbonic anhydrase enzyme center (CA) and a derivative of fullerene as a nanoscale inhibitor (C60-Inh) has been investigated, based on, B3LYP level, using 6-31G* basis set. The results of calculations indicate that this special fullerene derivative could be deprotonated from three different positions and interacts with CA active site to form three CA-C60-Inh complexes. The calculated results indicate that deprotonated inhibitor is coordinated to the Zn2+ ion and all the complexes have tetrahedral geometry. The calculated binding energy (BD) and complexation energy clearly show the complex between C60-Inh and CA active site from N13 position is more favorable than the other position. Also thermodynamic functions such as standard enthalpy of complexation (ΔH 0com ), standard entropy of complexation (ΔS 0com ) and standard Gibbs free energy of complexation (ΔG 0com ) for three CA-inhibitor complexes are evaluated. In order to approach the ideal geometry and provide further insight into the different complexation properties, the single point calculation at the B3LYP/6-311G** level have been used for all three different complexes to confirm the results of B3LYP/6-31G*. Thus, fullerene derivatives show a new class of nano scale carbonic anhydrase inhibitors that might find applications for targeting physiologically relevant isoforms of different forms of CA.