title: Signatures of n→π* interactions in proteins.
abstract: The folding of proteins is directed by a variety of interactions, including hydrogen bonding, electrostatics, van der Waals' interactions, and the hydrophobic effect. We have argued previously that an n→π* interaction between carbonyl groups be added to this list. In an n→π* interaction, the lone pair (n) of one carbonyl oxygen overlaps with the π* antibonding orbital of another carbonyl group. The tendency of backbone carbonyl groups in proteins to engage in this interaction has consequences for the structures of folded proteins that we unveil herein. First, we employ density functional theory to demonstrate that the n→π* interaction causes the carbonyl carbon to deviate from planarity. Then, we detect this signature of the n→π* interaction in high-resolution structures of proteins. Finally, we demonstrate through natural population analysis that the n→π* interaction causes polarization of the electron density in carbonyl groups and detect that polarization in the electron density map of cholesterol oxidase, further validating the existence of n→π* interactions. We conclude that the n→π* interaction is operative in folded proteins.
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Newberry
authors.forename: Gail J
authors.initials: GJ
authors.lastname: Bartlett
authors.forename: Brett
authors.initials: B
authors.lastname: VanVeller
authors.forename: Derek N
authors.initials: DN
authors.lastname: Woolfson
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Raines
mesh_terms: D002789:Cholesterol Oxidase / Q000737:chemistry; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D015203:Reproducibility of Results; D055672:Static Electricity
chemical_list: D011506:Proteins; D002789:Cholesterol Oxidase
keywords: Bürgi-Dunitz trajectory; electron density; hyperconjugation; pyramidalization; stereoelectronic effect