Protein structural codes and nucleation sites for protein folding

One of the long-standing controversial arguments in protein foldingis Levinthal's paradox. We have recently proposed a new nucleationhypothesis and shown that the nucleation residues are the mostconserved sequences in protein. To avoid the complicated effect oftertiary interactions, we limit our search for structural codes tothe nucleation residues. Starting with the hypotheses of secondarystructure nucleation and conservation of residues important forfolding, we have analysed 762 folds classified as unique by SCOP.Segments of 17 residues around the top 20% conserved amino acids areanalysed, resulting in approximately 100 clusters each for the mainsecondary structure classes of helix, sheet and coil. Helicalclusters have the longest correlation range, coils the shortest (fourresidues). Strong specific sequence-structure correlation is observedfor coil but not for helix and sheet, suggesting a mappingrelationship between the sequence and the structure for coil. Wepropose that the central sequences in these clusters form `structuralcodes', a useful basis set for identifying nucleation sites, proteinfragments stable in isolation, and secondary structural patterns inproteins (particularly turns and loops).