Computational studies of immune stimulating complex (ISCOM) structure
Monash Institute of Pharmaceutical Sciences, Monash University.
Immune stimulating complexes (ISCOMs) are lipid nanoparticles mixtures of cholesterol, phospholipid, protein and saponin from the bark of Quillaja Saponiaria (the Chilean soap bark tree). ISCOMS, and the simpler ISCOM matrix (IMX) which lack protein, are complex systems with intriguing physical properties and biological properties, including applications as vaccine adjuvants. ISCOM and IMX particles consist of supramolecular structures, which appear from electron microscopy, to be ’holey’ spheres with a diameter of approximately 30 nm, although the precise structure of the IMX particles and the processes driving their formation are currently not well understood. We have used large-scale molecular dynamics simulations to model the formation of IMX particles and have developed models that are consistent with the experimental information available. Our models raise the prospect for the design of new, simpler saponin analogues for the development of biologically active lipid particles.