The overuse of antibiotics and fast evolution of bacteria with drug resistance in recent years pose great threaten to human beings’ health. β-Lactamases are proteins with main functions as hydrolyzing β-lactam based antibiotics. The fast evolution rate of β-lactamases is one of the reasons behind the antibiotic resistance crisis. Understanding β-lactamases’ hydrolysis mechanisms against antibiotics could pave the road to develop a theoretical model to predict the evolution of β-lactamases and provide hints to develop next generation of inhibitors with low resistance. In this project, reaction pathways of different types of β-lactamases: serine based β-lactamases and evolutionarily related penicillin binding protein were calculated using hybrid quantum mechanics and molecular mechanics within chain-of-states framework. The key structures along the catalytic reaction pathways of different β-lactamases were superimposed to reveal potential evolutionary relationship among these proteins. Additional analyses were carried out to further compare multiple reaction pathways and shed light on the evolution of catalytic mechanisms of serine β-lactamases.

Comparison of catalytic mechanisms of multiple β-lactamases: Seeking chemical driving force behind antibiotic resistance

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.