Aromatic side-chain interactions in proteins. II. Near- and far-sequence Phe-X pairs
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Updated: Sep 29, 2026

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Annick Thomas1, Rita Meurisse, Robert Brasseur
1Institut National de la Santé et de la Recherche Médicale Unité 410, Paris Cedex, France. thomas.a@fsagx.ac.be
Abstract:
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.
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