Insenstivity to close contacts and inability to predict protein foldability.

Mittal and coworkers recently (1) analyzed the spatial organization of folded proteins backbone and advocated an alternative hypothesis on protein folding stating that specific interactions among amino acids do not drive protein folding. The authors analyzed spatial distributions of Cα atoms for all amino acid pairs in about four thousands proteins available in PDB database and they found that the total number of contacts of an amino acid is correlated with the average occurrence of the amino acid. Their analysis led to a conclusion that there is no preferential neighborhood for an amino acid.