Abstract
Recent studies show that curcumin, a naturally fluorescent dye, can be used for the noninvasive optical imaging of retinal amyloid-fi (Afi) plaques. We investigated the molecular basis for curcumin???s specificity for hierarchical Afi structures using molecular dynamics simulations, with a focus on how curcumin is able to detect and discriminate different amyloid morphologies. Curcumin inhibits and breaks up fi-sheet formation in Afi monomers. With disordered Afi structures, curcumin forms a coarse-grained composite structure. With an ordered fibril, curcumin???s interaction is highly specific, and the curcumin molecules are deposited in the fibril groove. Curcumin tends to self-aggregate, which is finely balanced with its af inity for Afi. This tendency concentrates curcumin molecules at Afi deposition sites, potentially increasing the fluorescence signal. This is probably why curcumin is such an effective amyloid imaging agent.