Patterns in ionizable side chain interactions in protein structures

Daniele Gandini, Luca Gogioso, Martino Bolognesi, Domenico Bordo

Research output: Contribution to journalArticlepeer-review


In a selected set of 44 high-resolution, non-homologous protein structures, the intramolecular hydrogen bonds or salt bridges formed by ionizable amino acid side chains were identified and analyzed. The analysis was based on the investigation of several properties of the involved residues such as their solvent exposure, their belonging to a certain secondary structural element, and their position relative to the N- and C-termini of their respective structural element. It was observed that two-thirds of the interactions made by basic or acidic side chains are hydrogen bonds to polar uncharged groups. In particular, the majority (78%) of the hydrogen bonds between ionizable side chains and main chain polar groups (sch:mch bonds) involved at least one buried atom, and in 42% of the cases both interacting atoms were buried. In α-helices, the sch:mch bonds observed in the proximity of the C- and N-termini show a clear preference for acidic and basic side chains, respectively. This appears to be due to the partial charges of peptide group atoms at the termini of α-helices, which establish energetically favorable electrostatic interactions with side chain carrying opposite charge, at distances even greater than 4.5 Å. The sch:mch interactions involving ionizable side chains that belong either to β- strands or to the central part of α-helices are based almost exclusively on basic residues. This results from the presence of main chain carbonyl oxygen atoms in the protein core which have unsatisfied hydrogen bonding capabilities.

Original languageEnglish
Pages (from-to)439-449
Number of pages11
JournalProteins: Structure, Function and Genetics
Issue number4
Publication statusPublished - 1996


  • hydrogen bonds
  • ionizable side chains
  • salt bridges
  • secondary structure

ASJC Scopus subject areas

  • Genetics
  • Structural Biology
  • Biochemistry


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