LAUSR

Abstract Enzyme I (EI) of bacterial phosphotransferase system is involved in the first step of the carbohydrate metabolism pathway. Due to its importance in bacterial survival and low similarity with human proteins, EI is an attractive drug target. With the aid of Computer Aided Drug Designing tools, we studied EI of Staphylococcus epidermidis, which recently adopted itself as a major etiological agent in discerning the cause of multi-drug resistant nosocomial infections of implanted medical devices. Due to a non-existent crystal structure, a high quality homology model of EI is predicted. Molecular docking analysis of potential inhibitors into the active site of the protein is performed and the best inhibitor is selected with according to the highest GoldScore (76.53). The protein-ligand complex was conducted through a 100 ns MD simulation. The trajectory analysis reveals that the N-terminal domain (EIN) and the P-His domain residues exhibited the greatest conformational changes while the active site shows minimum residual fluctuations and is considered as the most stable domain. The rigid body motions of EIN and P-His domain are recorded to be at their highest during the 35th and 83rd ns with highest RMSD values. Despite the highly flexible ‘personality’ of EI, the ligand remains tightly associated with the active site residues. The current lead compound holds potential as an effective drug against S. epidermidis which could be further tested in clinical settings. The dynamic nature of EI disclosed via MD simulation, can be further explored to understand the molecular kinetics of chemical reactions involved in the dedicated role of the protein would assist in better design of drugs in future.