Computational Modeling of the Binding of Amyloid-Beta to Neprilysin for Facilitating the Development of a Potential Alzheimer's Disease Therapy
Chemistry and Biochemistry
Bayer School of Natural and Environmental Sciences
Alzheimer's, Amyloid beta, Computer, model, Molecular dynamic, Neprilysin
The zinc metalloprotease neprilysin (NEP) has been shown to degrade small bioactive peptides. Crystal structures of seven NEP-inhibitor complexes and biochemical characterization of NEP activity have highlighted amino acid interactions that are crucial to ligand binding. Studies also indicate that NEP is one of a select group of metalloenzymes that degrade the amyloid-beta peptide (AÃƒÅ¸) in vivo and in situ. Accumulation of neurotoxic AÃƒÅ¸ aggregates in the brain appears to be a causative agent in the pathophysiology of Alzheimer's Disease (AD). For this reason the enzymatic degradation of AÃƒÅ¸ has been studied extensively, but little is known about specific binding interactions underlying NEP degradation of AÃƒÅ¸. Using known crystal structures of NEP, we have conducted comparative computational studies of ligand binding that predict NEP residues Arg 102 and 110 form binding interactions specific to AÃƒÅ¸. These interactions may provide insight for using NEP degradation of AÃƒÅ¸ in AD therapy.
Pope, D. (2013). Computational Modeling of the Binding of Amyloid-Beta to Neprilysin for Facilitating the Development of a Potential Alzheimer's Disease Therapy (Master's thesis, Duquesne University). Retrieved from https://dsc.duq.edu/etd/1507