ADDING BACKBONE TO PROTEIN-FOLDING - WHY PROTEINS ARE POLYPEPTIDES

It is argued that the chemical nature of the polypeptide backbone is t he central determinant of the three-dimensional structures of proteins . The requirement that buried polar groups form intramolecular hydroge n bonds limits the fold of the backbone to the well known units of sec ondary structure while the amino acid sequence chooses among the set o f conformations available to the backbone. 'Sidechain-only' models, ba sed for example on hydrophobicity patterns, fail to account for the pr operties of the backbone and thus will have difficulty capturing essen tial features of a folding pathway. This is evident from the incorrect predictions they make for the conformations of the limiting cases of all-hydrophobic or all polar sequences. (C) Current Biology Ltd