LAUSR

Abstract Semi-empirical SCC-DFTB based QM modelling is reported for the active site of human carbonic anhydrase II (HCA II), an enzyme having a rate determining proton transfer reaction with a rate constant of 106 s−1. In view of known limitations of SCC-DFTB, a detailed bench-marking of the SCC-DFTB results has been carried out against higher order density functional based theories using reactivity and time averaged network connections of the active site, derived from geometry optimization and QM/MM MD simulations. Bond lengths in the first coordination shell of Zn(II) ion, estimated using SCC-DFTB, are found to agree well with known EXAFS data. Other successful predictions include different reactivity descriptors, distribution of water around Zn(II) ion at the active site up to a separation of 5 A and the persistence of similar water network for the key proton transfer step.