Promising antibacterials for LLM of Staphylococcus aureus using virtual screening, molecular docking, dynamics, and MMPBSA

Abstract

In S. aureus, lipophilic membrane (LLM) protein is a methicillin resistance factor and is an essential role in peptidoglycan metabolism. The virtual screening of antibacterial molecules against the model of LLM was performed to identify the potent antibacterial molecules. Molecular docking results of pharmacokinetic filtered molecules illustrated that five molecules had higher binding affinities than tunicamycin (TUM) and were stabled via non-covalent interactions (hydrogen bond and hydrophobic interactions) at the active site of LLM. Further, molecular dynamics results revealed that binding of identified antibacterial molecules with LLM resulted in stable LLM-inhibitor(s) complexes. Molecular Mechanics/Position-Boltzmann Surface Area (MMPBSA) analysis showed that LLM-inhibitor(s) complexes had high binding affinities in the range of −213.49 ± 2.24 to −227.42 ± 3.05 kJ/mol. The amino acid residues decomposition analysis confirmed that identified antibacterial molecules bound at the active site (Asn148, Leu149, Asp151, Asp208, His269, His271, and His272) of LLM. Noticeably, the current study found five antibacterial molecules (BDE 27575101, BDE 33638168, BDE 33672484, LAS 51502073, and BDE 25098678) were highly potent than TUM and even than earlier reported molecules. Therefore, here reported antibacterial molecules may be used directly or developed to inhibit LLM of S. aureus.

Communicated by Ramaswamy H. Sarma

Keywords:

• Methicillin-resistant Staphylococcus aureus
• LLM
• molecular docking
• molecular dynamics simulation
• MMPBSA

Acknowledgment

Authors thankful to NMRbox (National Center for Biomolecular NMR Data Processing and Analysis, supported by NIH grant no. P41GM111135 (NIGMS)) to provide the computational facility for molecular dynamics work.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

The author(s) reported there is no funding associated with the work featured in this article.