title: Nature of amide carbonyl--carbonyl interactions in proteins.
abstract: Noncovalent interactions define and modulate biomolecular structure, function, and dynamics. In many protein secondary structures, an intimate interaction exists between adjacent carbonyl groups of the main-chain amide bonds. As this short contact contributes to the energetics of protein conformational stability as well as protein-ligand interactions, understanding its nature is crucial. The intimacy of the carbonyl groups could arise from a charge-charge or dipole-dipole interaction, or n-->pi * electronic delocalization. This last putative origin, which is reminiscent of the Burgi-Dunitz trajectory, involves delocalization of the lone pairs (n) of the oxygen (O(i-1)) of a peptide bond over the antibonding orbital (pi*) of the carbonyl group (C(i)=O(i)) of the subsequent peptide bond. By installing isosteric chemical substituents in a peptidic model system and using NMR spectroscopy, X-ray diffraction analysis, and ab initio calculations to analyze the consequences, the intimate interaction between adjacent carbonyl groups is shown to arise primarily from n-->pi* electronic delocalization. This finding has implications for organic, biological, and medicinal chemistry.
authors.affiliation: Graduate Program in Biophysics, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Choudhary
authors.forename: Deepa
authors.initials: D
authors.lastname: Gandla
authors.forename: Grant R
authors.initials: GR
authors.lastname: Krow
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Raines
mesh_terms: D000577:Amides / Q000737:chemistry*; D004583:Electrons; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D000577:Amides; D011506:Proteins