Loop folds in proteins and evolutionary conservation of folding nuclei

We show that loops of close contacts involving hydrophobic residues are important in protein folding. Contrary to 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.