Investigation of TEM-1 and SHV-1 beta-lactamase ligand binding

The abuse, overuse and misuse of beta-lactam antibiotics in treating bacterial infections have caused bacteria to develop resistance against them. One common antibiotic resistance mechanism utilized by bacteria is the production of beta-lactamase enzymes that cleave the amide bond in beta-lactam ring rendering the antibiotic ineffective. One way to combat this problem is to use beta-lactamase inhibitors in combination with beta-lactam antibiotics. Beta-lactamase inhibitor protein (BLIP) is an effective inhibitor of class A beta-lactamases such as TEM-1 and SHV-1. In the current research, the binding of BLIP to TEM-1 and to SHV-1 beta lactamase was investigated using molecular dynamics simulations. The binding free energies of BLIP complex with TEM-1 and SHV-1 betalactamases were calculated using Molecular Mechanic Poisson Bolztmann Surface Area (MM-PBSA) methodology. It was found that BLIP has significant differences in binding affinities toward TEM-1 and SHV-1 beta-lactamases.