Molecular modelling : the role of zinc ion in transition state of class B ß-lactamase hydrolysis of penicillins

Abstract

The focus of this research is computational work on the initial, transition and final state of class B ß- lactamase hydrolysis of penicillin and the role of zinc ions with various theoretical models using a variety of basis sets. The model includes semi-empirical, Hartree-Fock (HF), and density functional (DFT), and MP2 (Moller Plesset) theory in the Spartan Pro TM, 2004 TM program suite. The role of zinc ions in ß- lactamase enzyme was reflected by observing its effects on reducing the activation energies. Activiation energies were computed for ß- lactam ring, ß- lactam thiol ring, benyl Penicillin and various transition state complexes involved in concerted reaction, both with and without zinc ions. The corresponding values are for ß- lactam ring (7.88 to 56.72), ß- lactam thiol ring (18.10 to 69.10), and benzyl Penicillin (11.87 to 13.16) kcal/mol of reduction in Ea due to zinc ions, with different levels of semi-empirical, Hartree-Fock, and density functional theories and complexity of the mechanism. A simplified mimic of the active site was optimized by different levels of theory and the geometry of it was in accord, with that found by X-ray diffraction experiments of the crystal.