Arvi Rauk

I have been studying the chemistry underlying Alzheimer’s disease for more than a decade and have written two reviews. Most of the chemistry of AD involves the beta amyloid peptide (Ab).  It binds Cu and Fe with elevated redox activity and generates reactive oxygen species.  We have examined the metal binding and redox activity in great detail in silico, using the full gamut of computational methodology. Secondly, Ab undergoes a major conformational change from helical to beta sheet and aggregates into neutotoxic oligomeric species.  My group has expended considerable effort at designing inhibitors that are specific to Ab and inhibit its aggregation.  Ab is conformationally flexible and does not have a well-defined binding pocket unlike a normal enzyme which one may want to inhibit.  We have applied computer assisted drug design to design oligomerization inhibitiors for Ab [Samir Roy, PhD Dissertation, University of Calgary, 2010].  Some of these have been synthesized and assayed in a limited fashion.  As a result, I have a lot of experience in the biophysics and biochemistry of: protein/peptide interactions with metals, other proteins/peptides, and membranes; protein folding; oxidative damage to proteins (inflammation); lipid peroxidation. The research involves application of computational methodology ranging from computer assisted drug design, empirical molecular dynamics simulations of peptides and membranes, to high level ab initio computational chemistry.