On the Dependence of Prion and Amyloid Structure on the Folding Environment

Currently available analyses of amyloid proteins reveal the necessity of the existence of radical structural changes in amyloid transformation processes. The analysis carried out in this paper based on the model called fuzzy oil drop (FOD) and its modified form (FOD-M) allows quantifying the role of the environment, particularly including the aquatic environment. The starting point and basis for the present presentation is the statement about the presence of two fundamentally different methods of organizing polypeptides into ordered conformations—globular proteins and amyloids. The present study shows the source of the differences between these two paths resulting from the specificity of the external force field coming from the environment, including the aquatic and hydrophobic one. The water environment expressed in the fuzzy oil drop model using the 3D Gauss function directs the folding process towards the construction of a micelle-like system with a hydrophobic core in the central part and the exposure of polarity on the surface. The hydrophobicity distribution of membrane proteins has the opposite characteristic: Exposure of hydrophobicity at the surface of the membrane protein with an often polar center (as in the case of ion channels) is expected. The structure of most proteins is influenced by a more or less modified force field generated by water through the appropriate presence of a non-polar (membrane-like) environment. The determination of the proportion of a factor different from polar water enables the assessment of the protein status by indicating factors favoring the structure it represents.