IDENTIFICATION OF COMPACT, HYDROPHOBICALLY STABILIZED DOMAINS AND MODULES CONTAINING MULTIPLE PEPTIDE CHAINS

Compactness has been used to locate discontinuous structural units con taining one or more polypeptide chains in proteins of known structure. Rather than exhaustively calculating the compactness of all possible units, our procedure uses a screening algorithm to find discontinuous regions that are potentially compact. Precise calculations of compactn ess are restricted only to units in these regions. With our procedure, compactness can be used to discover discontinuous domains with virtua lly any number of disjoint peptides. Small, single-domain proteins may contain several compact regions: thus, compact regions do not always correspond to folding domains. Because a domain is an independent fold ing unit and should contain a hydrophobic core, compact units were fur ther examined for the presence of hydrophobic clusters (Zehfus MH, 199 5, Protein Sci 4:1188-1202). This added constraint limits the number o f acceptable units and helps greatly in the location of the true struc tural domains. The larger hydrophobically stabilized compact units cor respond to domains, while the smaller units may correspond to folding intermediates.