Simulation of two-dimensional ultraviolet spectroscopy of amyloid fibrils.

ABSTRACT: Revealing the structure and aggregation mechanism of amyloid fibrils is essential for the treatment of over 20 diseases related to protein misfolding. Coherent two-dimensional (2D) infrared spectroscopy is a novel tool that provides a wealth of new insight into the structure and dynamics of biomolecular systems. Recently developed ultrafast laser sources are extending multidimensional spectroscopy into the ultraviolet (UV) region, and this opens up new opportunities for probing fibrils. In a simulation study, we show that 2DUV spectra of the backbone of a 32-residue ?-amyloid (A?(9-40)) fibril associated with Alzheimer's disease and two intermediate prefibrillar structures carry characteristic signatures of fibril size and geometry that could be used to monitor its formation kinetics. The dependence of these signals on the fibril size and geometry is explored. We demonstrate that the dominant features of the ?-amyloid fibril spectra are determined by intramolecular interactions within a single A?(9-40), and intermolecular interactions at the "external interface" have clear signatures in the fine details of these signals.

SUBMITTER: Jiang J 

PROVIDER: S-EPMC2953465 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature