Other Biochemistry, Biophysics, and Structural Biology Commons^™

Computational Investigations Into Binding Dynamics Of Tau Protein Antibodies: Using Machine Learning And Biophysical Models To Build A Better Reality, Katherine Lee

University Scholar Projects

Misregulation of post-translational modifications of microtubule-associated protein tau is implicated in several neurodegenerative diseases including Alzheimer’s disease. Hyperphosphorylation of tau promotes aggregation of tau monomers into filaments which are common in tau-associated pathologies. Therefore, tau is a promising target for therapeutics and diagnostics. Recently, high-affinity, high-specificity single-chain variable fragment (scFv) antibodies against pThr-231 tau were generated and the most promising variant (scFv 3.24) displayed 20-fold increased binding affinity to pThr-231 tau compared to the wild-type. The scFv 3.24 variant contained five point mutations, and intriguingly none were in the tau binding site. The increased affinity was hypothesized to occur due …