Dynamic Analysis of Beta-lactamase Ligand Recognition

Abstract

A serious public health threat today is the emergence of pathogens that are resistant to commonly used antibiotics. One of the mechanisms of acquired drug resistance is the bacterial production of beta-lactamases, which break down these antibiotics. Currently used beta-lactamase inhibitors are not effective at targeting the 700 types and new mutants of beta-lactamases. Beta lactamase is therefore an important drug target in combating antibiotic resistance. Beta lactamase inhibitory protein (BLIP) is an effective inhibitor of TEM-1 and SHV-1, but binds and inhibits the two variants with different affinities. We hypothesize that elucidating the mechanism whereby the differential binding results will guide the design of new peptide inhibitors based on the BLIP structure. Molecular dynamics simulations are performed to examine the binding properties of BLIP and BLIP based peptides to TEM-1 and SHV-1 beta lactamase. These simulations on the complex will guide the design of new peptides.