• ß-strand;
  • ß-structure;
  • aromatic-aromatic interactions;
  • aromatic-peptide interactions;
  • profile analysis;
  • protein design;
  • protein folding;
  • protein modeling;
  • protein structure


Antiparallel β-sheets present two distinct environments to inter-strand residue pairs: βA, HB sites have two backbone hydrogen bonds; whereas at βA, 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 ßA, NHB site. In each case, the residues usually adopted sterically favored X1 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 ßA. HB site, one or both residues had to adopt less favored X1 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.