Insight into the Binding of First- and Second-Generation PET Tracers to 4R and 3R/4R Tau Protofibrils.

ABSTRACT: Primary supranuclear palsy (PSP) is a rare neurodegenerative disease that perturbs body movement, eye movement, and walking balance. Similar to Alzheimer's disease (AD), the abnormal aggregation of tau fibrils in the central neuronal and glial cells is a major hallmark of PSP disease. In this study, we use multiple approaches, including docking, molecular dynamics, and metadynamics simulations, to investigate the binding mechanism of 10 first- and second-generations of PET tracers for PSP tau and compare their binding in cortical basal degeneration (CBD) and AD tauopathies. Structure-activity relationships, binding preferences, the nature of ligand binding in terms of basic intermolecular interactions, the role of polar/charged residues, induced-fit mechanisms, grove closures, and folding

SUBMITTER: Li J 

PROVIDER: S-EPMC10515481 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature