n-->pi* interactions in proteins

Nat Chem Biol. 2010 Aug;6(8):615-20. doi: 10.1038/nchembio.406. Epub 2010 Jul 11.


Hydrogen bonds between backbone amides are common in folded proteins. Here, we show that an intimate interaction between backbone amides also arises from the delocalization of a lone pair of electrons (n) from an oxygen atom to the antibonding orbital (pi*) of the subsequent carbonyl group. Natural bond orbital analysis predicted significant n-->pi* interactions in certain regions of the Ramachandran plot. These predictions were validated by a statistical analysis of a large, non-redundant subset of protein structures determined to high resolution. The correlation between these two independent studies is striking. Moreover, the n-->pi* interactions are abundant and especially prevalent in common secondary structures such as alpha-, 3(10)- and polyproline II helices and twisted beta-sheets. In addition to their evident effects on protein structure and stability, n-->pi* interactions could have important roles in protein folding and function, and merit inclusion in computational force fields.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology
  • Crystallography, X-Ray
  • Databases, Nucleic Acid
  • Dipeptides / chemistry
  • Hydrogen Bonding*
  • Models, Molecular
  • Protein Conformation*
  • Protein Structure, Secondary
  • Proteins / chemistry*


  • Dipeptides
  • Proteins