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Figure 9.7
A hierarchical condensation model for protein folding. Sequence
determines secondary structure, and secondary structure elements
assemble to form an approximate tertiary structure. Energy
refinement yields a detailed three-dimensional  structure.

five residues. Presumably, the solution is that the conformation of some sequences is specified in large part by local interactions, while others are stable only in the context of the neighboring sequences. The most difficult challenge for secondary structure prediction methods is to determine the structure of these context-dependent regions.

Two general strategies have been applied to the secondary structure prediction problem: statistical approaches and rule-based approaches.

The statistical approaches assert that proteins of known tertiary structure provide a useful data set describing secondary structure preferences of individual amino acids. Two presumptions are made: tertiary structure will exert no consistent effects on secondary structure, and the existing database is of sufficient size to provide important information. The first assertion recalls our discussion of the local versus global determinants of protein organization believe that local nteractions play a significant role in protein folding, but, in the literature,