Molecular dynamics of the membrane interaction and localisation of prodigiosin

Abstract

The tripyrrolic antibiotic prodigiosin causes diverse reactions on its targets like energy spilling, membrane leakage, loss of motility and phototoxicity. It has bacteriostatic, bactericidal, anti-fungal, anti-cancer and immunosuppressive properties. Most of the functions suggest the role of prodigiosin in membrane disruption but the exact mechanism remains unknown. A molecular dynamics study was performed to understand the interactions of prodigiosin with the membrane. It was seen that prodigiosin from the solvent enters the membrane immediately either individually or as small clusters. Prodigiosin clusters with more than eight molecules do not appear to enter the membrane. Upon entry, the molecules orient themselves along the membrane-water interface with the pyrrole rings interacting with lipid head groups and with water. This orientation is stabilised by hydrogen bonding and hydrophobic interactions. The presence of prodigiosin molecules in the membrane changes the local lipid architecture and reduces the solvent accessibility of the membrane. The membrane fluidity, thickness or area per lipid head are largely unaffected. This suggests that prodigiosin could cause most damage in the vicinity of a membrane protein and thus could also explain the reason for varied effects on the targets.