Hydrogen bonds with pi-acceptors in proteins: frequencies and role in stabilizing local 3D structures

J Mol Biol. 2001 Jan 19;305(3):535-57. doi: 10.1006/jmbi.2000.4301.


A comprehensive structural analysis of X--H...pi hydrogen bonding in proteins is performed based on 592 published high-resolution crystal structures (< or = 1.6 A). All potential donors and acceptors are considered, including acidic C--H groups. The sample contains 1311 putative X--H...pi hydrogen bonds with N--H, O--H or S--H donors, that is about one per 10.8 aromatic residues. By far the most efficient pi-acceptor is the side-chain of Trp, which accepts one X--H...pi hydrogen bond per 5.7 residues. The focus of the analysis is on recurrent structural patterns involving regular secondary structure elements. Numerous examples are found where peptide X--H...pi interactions are functional in stabilization of helix termini, strand ends, strand edges, beta-bulges and regular turns. Side-chain X--H...pi hydrogen bonds are formed in considerable numbers in alpha-helices and beta-sheets. Geometrical data on various types of X--H...pi hydrogen bonds are given.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon / chemistry
  • Carbon / metabolism
  • Crystallography, X-Ray
  • Databases as Topic
  • Humans
  • Hydrogen / chemistry
  • Hydrogen / metabolism
  • Hydrogen Bonding*
  • Models, Molecular
  • Protein Structure, Secondary
  • Proteins / chemistry*
  • Proteins / metabolism
  • Thermodynamics
  • Tryptophan / metabolism
  • Water / chemistry
  • Water / metabolism


  • Proteins
  • Water
  • Carbon
  • Hydrogen
  • Tryptophan