Molecular Dynamics of Mycolic Acid Monolayers

Mycobacterium tuberculosis, the organism responsible for TB infection in humans, is inherently resilient against host defences and anti-TB drugs. This persistence is attributed partly to the presence of lipids, such as mycolic acids (MAs), which make the cell wall impermeable. To study the conformational dynamics of MAs, we present a coarse-grained model for a representative α-MA (AMA) from Mycobacterium tuberculosisusing the MARTINI force field. The model is used to simulate monolayers of different sizes; a small monolayer consisting of 220 MAs and a large monolayer consisting of 1972 MAs. The model could replicate key features of experimental monolayers such as phase changes and the collapse point. By studying the conformation of MAs in the simulated monolayers, it was found that AMA did not fold into the W-conformation at large surface areas but was only folded at the head group to give a wide U-shape. On monolayer compression, the MA chains came closer together, into a narrower U-shape, and an ordered monolayer was formed before it collapsed.