Folding of linear chains of amino acids, i.e., bioproteins and synthetic peptides, is, for single-domain macromolecules, accompanied by the formation of secondary structures (helices, sheets, turns) and the tertiary hydrophobic-core collapse. While secondary structures are typically localized and thus limited to segments of the peptide, the effective hydrophobic interaction between nonbonded, nonpolar amino acid side chains results in a global, cooperative arrangement favoring folds with compact hydrophobic core and a surrounding polar shell that screens the core from the polar solvent. Systematic analyses for unraveling general folding principles are extremely difficult in microscopic all-atom approaches, since the folding process is strongly dependent on the “disordered” sequence of amino acids and the native-fold formation is inevitably connected with, at least, significant parts of the sequence. Moreover, for most proteins, the folding process is relatively slow (microseconds to seconds), which is due to a complex, rugged shape of the freeenergy landscape [190–192] with “hidden” barriers, depending on sequence properties. Although there is no obvious system parameter that allows for a general description of the accompanying conformational transitions in folding processes (as, for example, the reaction coordinate in chemical reactions), it is known that there are only a few characteristic folding behaviors known, such as two-state folding, folding through intermediates, and glass-like folding into metastable conformations [193–199].

Thus, if a classification of folding characteristics is useful at all, strongly simplified coarse-grained models should allow to describe generic statistical [46,47] and kinetic [200] pseudo-universal properties.