On the satisfaction of backbone-carbonyl lone pairs of electrons in protein structures

Gail J Bartlett, Derek N Woolfson

Research output: Contribution to journalArticle (Academic Journal)peer-review

20 Citations (Scopus)
444 Downloads (Pure)


Protein structures are stabilized by a variety of non-covalent interactions (NCIs), including the hydrophobic effect, hydrogen bonds, electrostatic forces and van der Waals' interactions. Our knowledge of the contributions of NCIs, and the interplay between them remains incomplete. This has implications for computational modeling of NCIs, and our ability to understand and predict protein structure, stability and function. One consideration is the satisfaction of the full potential for NCIs made by backbone atoms. Most commonly, backbone-carbonyl oxygen atoms located within α-helices and β-sheets are depicted as making a single hydrogen bond. However, there are two lone pairs of electrons to be satisfied for each of these atoms. To explore this, we used operational geometric definitions to generate an inventory of NCIs for backbone-carbonyl oxygen atoms from a set of high-resolution protein structures and associated molecular-dynamics simulations in water. We included more-recently appreciated, but weaker NCIs in our analysis, such as n→π* interactions, Cα-H bonds and methyl-H bonds. The data demonstrate balanced, dynamic systems for all proteins, with most backbone-carbonyl oxygen atoms being satisfied by two NCIs most of the time. Combinations of NCIs made may correlate with secondary structure type, though in subtly different ways from traditional models of α- and β-structure. In addition, we find examples of under- and over-satisfied carbonyl-oxygen atoms, and we identify both sequence-dependent and sequence-independent secondary-structural motifs in which these reside. Our analysis provides a more-detailed understanding of these contributors to protein structure and stability, which will be of use in protein modeling, engineering and design.

Original languageEnglish
Pages (from-to)887-897
Number of pages11
JournalProtein Science
Issue number4
Early online date25 Feb 2016
Publication statusPublished - Apr 2016

Structured keywords

  • Bristol BioDesign Institute
  • BrisSynBio


  • protein folding
  • protein structure
  • protein stability
  • bioinformatics
  • hydrogen bonding
  • noncovalent interactions
  • n => π* interactions


Dive into the research topics of 'On the satisfaction of backbone-carbonyl lone pairs of electrons in protein structures'. Together they form a unique fingerprint.

Cite this