Simulation study of the structure and dynamics of the Alzheimer's amyloid peptide congener in solution

The amyloid A beta (10-35)-NH2 peptide is simulated in an aqueous environme nt on the nanosecond time scale. One focus of the study is on the validatio n of the computational model through a direct comparison of simulated stati stical averages with experimental observations of the peptide's structure a nd dynamics. These measures include (1) nuclear magnetic resonance spectros copy-derived amide bond order parameters and temperature-dependent H-alpha, proton chemical shifts, (2) the peptide's radius of gyration and end-to-en d distance, (3) the rates of peptide self-diffusion in water, and (4) the p eptide's hydrodynamic radius as measured by quasielastic light scattering e xperiments. A second focus of the study is the identification of key intrap eptide interactions that stabilize the central structural motif of the pept ide. Particular attention is paid to the structure acid fluctuation of the central LVFFA hydrophobic cluster (17-21) region and the VGSN turn (24-27) region. There is a strong correlation between preservation of the structure of these elements and interactions between the cluster and turn regions in imposing structure on the peptide monomer. The specific role of these inte ractions in relation to proposed mechanisms of amyloidosis is discussed.