Analysis of Electrostatic Interaction between Dimer Complexes. Part II: Criteria and Conditions on Inhibitors of APP Protein Derivatives

Abstract

We communicate the results of calculations and selection methods, and identify the properties, of inhibitors that block the formation of high-molecular-weight structures from amyloid peptides, with their blocking mechanism explained. We consider in detail the biochemical requirements for, and the criteria and conditions for identification of, inhibitors that prevent amyloids from forming higher-order structures. For the inhibitors, we investigate modified peptides that, by combining with amyloid peptides, will form stable dimers thereby preventing amyloids from participating in ever different and new biochemical reactions. We address biochemical reactions of the amyloids with amyloid peptides of a similar kind, but their possible interaction with blood vessel walls is beyond the scope of this work. For the criterion of dimer complex stability, we use (i) logarithm of the condition number of potential energy matrix of paired electrostatic interaction between amino acid residues and (ii) the differential entropy of a multidimensional normal distribution.