Designing DapE- Inhibitors through Molecular Dynamic Simulations

Abstract

Development of new classifications of inhibitors are essential in order to control infectious diseases. Currently the only antibiotics available follow two approaches: inhibition of cell wall remodeling and protein synthesis. DapE is part of the succinylase biosynthetic pathway and is important to the production of lysine and mDap (meso-diaminopimelate) both of which synthesize protein and bacterial peptidoglycan cell wall remodeling. Due to increasing bacterial resistance, a new method of treatment is critical through inhibition of the enzymatic activity of DapE. There is no evidence of DapE in mammals, therefore, inhibition should be selective in thwarting bacterial growth. High-Throughput Screening (HiTS) was utilized to screen over 33,000 different compounds which identified several inhibitors of DapE. Computational chemistry uses the x-ray determined structure of DapE to perform molecular docking. The application of this process could lead to the discovery of other possible inhibitors as new antibiotics