35th Annual Student Research Conference
Computational Investigation of the Aducanumab Antibody in its Binding to Amyloid-β Species Associated with Alzheimer’s Disease
Jonathan C. Bradfield
Dr. Bill R. Miller, Faculty Mentor
Alzheimer’s disease (AD) is a neurodegenerative disease that is the 6th leading cause of death in the US. One AD pathology outlines the formation of Amyloid-β (Aβ) protein aggregates in the neural synapse that lead to decreased synapse number and activity which causes memory loss. Aducanumab was recently granted FDA approval for the treatment of AD, though its clinical efficacy has shown mixed results. Aducanumab is a monoclonal antibody that binds to Aβ and clears it from the neural synapse. Aducanumab has also shown a specificity towards aggregate forms of Aβ, and any binding to monomeric species decreases Aducanumab’s efficiency. Molecular Dynamics simulations were run on the Aβ epitope, Aβ monomers, and Aβ pentamers to identify favorable interactions between Aducanumab and these different Aβ species. In these simulations, Aducanumab bound more favorably to less sterically constrained monomeric Aβ species due to favorable interactions outside of the binding pocket.
Keywords: Alzheimer's Disease, Biochemistry, Neuroscience, Immunology, Computational Biophysics, Aducanumab, Amyloid-Beta, Aduhelm
Topic(s):Biochemistry and Molecular Biology
Biology
Chemistry
Presentation Type: Oral Presentation
Session: 105-1
Location: MG 2001
Time: 8:30