----------------------------------------------------------------------- BIOINFORMATICS COLLOQUIUM School of Computational Sciences George Mason University ----------------------------------------------------------------------- Assembly of Alzheimer's Abeta_16-22 oligomers: A molecular dynamics study Dmitri Klimov University of Maryland Friday, March 26, 2004 4:30 pm Verizon Auditorium, Prince William Campus Alzheimer's disease is associated with aggregation of Abeta peptides into amyloid fibrils, but biophysical understanding of the kinetics of Abeta oligomerization and fibril formation is still lacking. In this talk I present the results of molecular dynamics study of aggregation of Abeta16-22 fragments from Alzheimer's Abeta peptide. For the first time the formation of Abeta oligomers is observed in silica, starting with random initial conditions. Upon oligomerization interpeptide interactions trigger dramatic conformational changes. Oligomer formation is found to proceed through an obligatory helical intermediate, which later gradually converts into antiparallel beta-structure similar to that observed in the experiments. Aggregation of Abeta16-22 peptides is initially driven by hydrophobic interactions, while electrostatic interactions, which form later, confer an antiparallel registry of beta-structure. The proposed kinetic mechanism of Abeta oligomerization is consistent with experiments and may represent an universal pathway of amyloid fibril formation. The roles of Abeta sequence and environmental factors (denaturants) are also discussed. ---------------------------------------------------------------------- Refreshments are served at 4:00 pm. Find the schedule and directions at http://www.binf.gmu.edu/colloq.html