3D structures of membrane-associated small molecules as determined in isotropic bicelles

About half of known bioactive organic molecules, including drugs, are known to target biological membranes and membrane proteins. Despite this, it has proven difficult to define the membrane-bound conformations of these molecules. In recent years, bicelles have been recognized as a more appropriate membrane model than micelles because their planar portion is composed of a lipid bilayer. Bicelles with a small diameter, termed isotropic or fast-tumbling bicelles, allow for high-resolution NMR measurements due to their high mobility in suspension, and therefore have become a versatile tool for structure studies of membrane-associated molecules. Following a brief description of the morphology and preparation of isotropic bicelles, we summarize their application to structural studies of membrane-bound peptides and small molecules, and then highlight our recent studies on the 3D structures of erythromycin A, salinomycin and amphidinol 3 using isotropic bicelles.