Amyloidogenic determinants are usually not buried

It appears that the consensus prediction tool is slightly more objective than individual prediction methods alone and suggests several previously not identified amino acid stretches as potential amyloidogenic determinants, which (although several of them may be overpredictions) require further experimental studies. The tool is available at: http://biophysics.biol.uoa.gr/AMYLPRED webcite. Utilizing molecular graphics programs, like O and PyMOL, as well as the algorithm DSSP, it was found that nearly all experimentally verified amyloidogenic determinants (short peptide stretches favouring aggregation and subsequent amyloid formation), and several predicted, with the aid of the tool AMYLPRED, but not experimentally verified amyloidogenic determinants, are located on the surface of the relevant amyloidogenic proteins. This finding may be important in efforts directed towards inhibiting amyloid fibril formation.The most significant result of this work is the observation that virtually all, to date, experimentally determined amyloidogenic determinants and the majority of predicted, but not yet experimentally verified short amyloidogenic stretches, lie 'exposed' on the surface of the relevant amyloidogenic proteins, and also several of them have the ability to act as conformational 'switches'. Experiments, focused on these fragments, should be performed to test this idea.Amyloidoses are diseases that occur when soluble proteins undergo conformational re-arrangements and form fibrillar aggregates known as amyloid deposits. Such diseases include Alzheimer's, Parkinson's, Creutzfeldt-Jacob's and Huntington's neurodegenerative diseases, as well as type II diabetes, prion diseases and many more. Amyloidogenic proteins are quite diverse, with little similarity in sequence and native 3D-structure [1,2]. Additionally, several proteins and peptides not related to amyloidoses have also been shown to have the potential to form amyloid fibrils in vitro, suggesting that this ability fo