We show that loops of close contacts involving hydrophobic residues are important in protein folding. Contrary to Berezovsky Berezovsky and Trifonov (J. Biomol. Struct. Dyn. 20, 5-6, 2002) the loops important in protein folding usually are much larger in size than 23-31 residues, being instead comparable to the size of the protein for single domain proteins. Additionally what is important are not single loop contacts, but a highly interconnected network of such loop contacts, which provides extra stability to a protein fold and which leads to their conservation in evolution.

Key words: protein folding, Levinthal paradox, loop fold structure, closed loops, evolutionary conservation, folding nucleus.