How does the amino acid sequence code for the three-dimensional structure of the protein?
The initial steps in protein folding are the most relevant for the exploration of the link between sequence and folded structure. They are also the most difficult to study experimentally. We tackled this problem by using short peptide fragments of proteins as a model system for the earliest events in the folding process. The initial focus of this work was to determine the sequence specificity for residual structure in short peptides in solution, as a model system for secondary structure propensities in unfolded proteins that might act as folding initiation sites. Reverse turns were found to be highly sequence-dependent (Refs 9, 47, 87 from the Publication List), and in some cases contained a sufficiently high population of turn conformations that the structure of the turn could be calculated (48). In order to determine which parts of proteins potentially contained folding initiation sites, three large sets of peptides were studied, corresponding to the complete sequences (in pieces) of
