Three thousand eight hundred ninety-nine P-turns have been identified and classified using a nonhomologous data set of 205 protein chains. These were used to derive &turn positional potentials for turn types I' and 11' for the first time and to provide updated potentials for formation of the more common types I, 11, and VIII. Many of the sequence preferences for each of the 4 positions in turns can be rationalized in terms of the formation of stabilizing hydrogen bonds, preferences for amino acids to adopt a particular conformation in 4, rC. space, and the involvement of turn types I' and 11' in &hairpins. Only 1,632 (42%) of the turns occur in isolation; the remainder have at least 1 residue in common with another turn and have hence been classified as multiple turns. Several types of multiple turn have been identified and analyzed.

Methods have been developed to assess the stereochemical quality of any protein structure both globally and locally using various criteria. Several parameters can be derived from the coordinates of a given structure. Global parameters include the distribution of phi, psi and chi 1 torsion angles, and hydrogen bond energies. There are clear correlations between these parameters and resolution; as the resolution improves, the distribution of the parameters becomes more clustered. These features show a broad distribution about ideal values derived from high-resolution structures. Some structures have tightly clustered distributions even at relatively low resolutions, while others show abnormal scatter though the data go to high resolution. Additional indicators of local irregularity include proline phi angles, peptide bond planarities, disulfide bond lengths, and their chi 3 torsion angles. These stereochemical parameters have been used to generate measures of stereochemical quality which provide a simple guide as to the reliability of a structure, in addition to the most important measures, resolution and R-factor. The parameters used in this evaluation are not novel, and are easily calculated from structure coordinates. A program suite is currently being developed which will quickly check a given structure, highlighting unusual stereochemistry and possible errors.

We describe a suite of programs, PROMOTIF, that analyzes a protein coordinate file and provides details about the structural motifs in the protein. The program currently analyzes the following structural features: secondary structure; beta-and gamma-turns; helical geometry and interactions; beta-strands and beta-sheet topology; beta-bulges; beta-hairpins; beta-alpha-beta units and psi-loops; disulphide bridges; and main-chain hydrogen bonding patterns. PROMOTIF creates postscript files showing the examples of each type of motif in the protein, and a summary page. The program can also be used to compare motifs in a group of related structures, such as an ensemble of NMR structures.

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Antiparallel P-sheets present two distinct environments to inter-strand residue pairs: P A , H B sites have two backbone hydrogen bonds; whereas at PA,NHB positions backbone hydrogen bonding is precluded. We used statistical methods to compare the frequencies of amino acid pairs at each site. Only -10% of the 210 possible pairs showed occupancies that differed significantly between the two sites. Trends were clear in the preferred pairs, and these could be explained using stereochemical arguments. Cys-Cys, Aromatic-Pro, Thr-Thr, and Val-Val pairs all preferred the PA,NHB site. In each case, the residues usually adopted sterically favored X I conformations, which facilitated intra-pair interactions: Cys-Cys pairs formed disulfide bonds; Thr-Thr pairs made hydrogen bonds; Aromatic-Pro and Val-Val pairs formed close van der Waals contacts. In contrast, to make intimate interactions at a P A , H B site, one or both residues had to adopt less favored xI geometries. Nonetheless, pairs containing glycine and/or aromatic residues were favored at this site. Where glycine and aromatic side chains combined, the aromatic residue usually adopted the gauche-conformation, which promoted novel aromatic ring-peptide interactions. This work provides rules that link protein sequence and tertiary structure, which will be useful in protein modeling, redesign, and de novo design. Our findings are discussed in light of previous analyses and experimental studies.Keywords: P-strand; p-structure; aromatic-aromatic interactions; aromatic-peptide interactions; profile analysis; protein design; protein folding; protein modeling; protein structureThe amino acid sequence of a protein dictates the acquisition and stabilization of its active state (Anfinsen, 1973). Therefore, to improve understanding of protein folding and design, it is critical to establish rules that link sequence and structure. Studies in this area have revealed that context is a key determinant of the preference of a residue for a particular secondary structure. At an elementary level, patterns of hydrophobic ( H ) and polar (P) residues play roles in the organization of protein structures (Lim, 1974a(Lim, , 1974bDill, 1990; Huang et al., 1995;Sun et al., 1995;West & Hecht, 1995). For example, in soluble proteins, alternating, HPHP, patterns occur in @-strands, whereas a-helices show PHPPHHP and similar repeats. Such patterns produce amphipathic secondary structures, which can promote the organization of tertiary structure in globular proteins. However, there is no absolute requirement for such simple HP patterns in the secondary structures of proteins Reprint requests to: Dek Woolfson,