Abstract
It is well known that Alzheimer's disease (AD) is correlated with the aggregation of amyloid-beta (Aβ) peptides into plaques. Due to the large size of Aβ plaques (several mm), and long incubation period (hours and days), Molecular Dynamics (MD) simulations require coarse-grained models. Our model is based on the coarse-grained model of Fawzi et al [Biophysical J. 94 (2008) 2007-2016] that represents one amino acid as a single unit. However, the new model will include an improved representation of backbone-hydrogen bonds that stabilize the β-sheet structures of plaques. The van der Waals force interactions used in the model will be based on published NMR crystal structures of Aβ segments resolved by the Eisenberg group [Nature 447 (2007) 453-457]. MD simulations observed a rugged energy landscape, with cooperative monomer state to oligomers state, as the temperature is lowered. This is followed at lower temperature, by trapped states that lead slowly to crystal structures. Transition states and trapped states are identified using a metric that includes the radius of gyration of number of backbone hydrogen bonds.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
