Aromatic Side-Chain Interactions In Proteins. II. Near- And Far-Sequence Phe-X Pairs

We have collected all aromatic pairs (3152) involving an N-phenyl partner in a
dataset of 593 proteins of the PDB: 728 of these pairs involve a partner residue
less than 6 apart in the sequence. These near-sequence Phe-X pairs correspond to
specific conformations that stabilize secondary structures, mainly alpha-helices
when the residues are 1, 3, and 4 apart, and beta-strands when they are 2 apart
in the sequence. These conformations are not spatially random and have been
examined in detail. The remaining phenylalanine pairs (2424) are between partners
more than 5 apart in the sequence. Of these far-sequence pairs, 34% of
occurrences are in sheets. Next in frequencies are pairs that bridge a
beta-strand to a helix (24%), followed by pairs that bridge a beta-strand to a
random coiled structure (15%). Helix to helix pairs only constitute 12% of these
far-sequence pairs. Analysis of the pairing frequency supports the hypothesis
that aromatic interactions are late events of protein folding.