Molecular Modeling and Simulation of the Peptidoglycan Layer of Gram-Positive Bacteria Staphylococcus aureus

The peptidoglycan (PG) layer is a vital component of
the bacterial
cell wall that protects the cell from rupturing due to internal pressure.
Its ubiquity across the bacterial kingdom but not animals has made
it the target of drug discovery efforts. The PG layer composed of
cross-linked PG strands is porous enough to allow the diffusion of
molecules through the PG mesh and into the cell. The lack of an accurate
atomistic model of the PG mesh has limited the computational investigations
of drug diffusion in Gram-positive bacteria, which lack the outer
membrane but consist of a much thicker PG layer compared to Gram-negative
bacteria. In this work, we built an atomistic model of the Staphylococcus aureus PG layer architecture with
horizontally aligned PG strands and performed molecular dynamics simulations
of the diffusion of curcumin molecules through the PG mesh. An accurate
model of the Gram-positive bacterial cell wall may aid in developing
novel antibiotics to tackle the threat posed by antibiotic resistance.