DETERMINANTS OF STRAND REGISTER IN ANTIPARALLEL BETA-SHEETS OF PROTEINS

Antiparallel beta-sheets present two distinct environments to inter-st rand residue pairs: beta(A,HB) sites have two backbone hydrogen bands; whereas at beta(A,NHB) positions backbone hydrogen bonding is preclud ed. We used statistical methods to compare the frequencies of amino ac id pairs at each site. Only similar to 10% of the 210 possible pairs s howed occupancies that differed significantly between the two sites. T rends were clear in the preferred pairs, and these could be explained using stereochemical arguments. Cys-Cys, Aromatic-Pro, Thr-Thr, and Va l-Val pairs all preferred the beta(A,NHB) site. In each case, the resi dues usually adopted sterically favored chi(1) conformations, which fa cilitated intra-pair interactions: Cys-Cys pairs formed disulfide bond s; Thr-Thr pairs made hydrogen bonds; Aromatic-Pro and Val-Val pairs f ormed close van der Waals contacts. In contrast, to make intimate inte ractions at a beta(A,HB) site, one or both residues had to adopt less favored chi(1) geometries. Nonetheless, pairs containing glycine and/o r aromatic residues were favored at this site. Where glycine and aroma tic side chains combined, the aromatic residue usually adopted the gau che(-) conformation, which promoted novel aromatic ring-peptide intera ctions. This work provides rules that link protein sequence and tertia ry structure, which will be useful in protein modeling, redesign, and de nova design. Our findings are discussed in light of previous analys es and experimental studies.