Graduate Student: Matthew Voelker
Abstract: Alzheimer's Disease is strongly associated with small oligomeric assemblies formed by amyloid b-protein (ABeta), in particular with the 42 amino acids-long ABeta1-42. Recently, ABeta1-42 oligomer structure has been characterized computationally by discrete molecular dynamics (DMD) combined with implicit-solvent intermediate-resolution protein model. In vivo, ABeta1-42 coexists with other proteins and biomolecules in a crowded environment. To understand the effects of crowding on ABeta1-42 assembly, we simulated ABeta1-42 oligomer formation in the presence of crowders using the DMD approach described above. Analysis of the resulting conformations yielded an increased number of lower-order oligomers for simulations containing crowders. The monomers, tetramers, pentamers, and hexamers we observed in the presence of crowders had more Beta-strands at the N-terminus and in the central region. These conformations also had an increase in the number of contacts between the C-terminus and central region, implying more compact monomers and oligomers. Monomers with crowders also had a notably larger number of contacts between the N-terminus and C-terminus. The increased content of Beta-strands and more compact monomers and oligomers we observed are in agreement with current theoretical predictions and experimental results regarding the effects of crowding upon protein assembly.
Advisor: Dr. Brigita Urbanc