In 1951, Linus Pauling first reported on the hydrogen bonds between backbone amides that are common in the a-helices and �-sheets of proteins. We have discovered an analogous interaction. This interaction arises from the delocalization of a lone pair of electrons (n) from an oxygen atom to the anti-bonding orbital (p*) of the subsequent carbonyl group in a polypeptide chain. The signature of this n?p* interaction is most evident in the pyramidalization of the acceptor carbonyl group. Our ab initio calculations predict significant n?p* interactions in certain regions of the Ramachandran plot. We have validated these predictions by a statistical analysis of a large, non-redundant subset of protein structures determined to high resolution. We find n?p* interactions to be especially abundant in common secondary structures such as a-, 310-, and polyproline II helices, and twisted �-sheets. n)(p Pauli repulsion attenuates the n?p* interaction with olefins and compromises their utility as peptidomimetics. In addition to their evident effects on peptide and protein conformation, n?p* interactions could play important roles in protein folding and function, and merit inclusion in computational force fields. Finally, we have identified important n?p* interactions within small molecules (such as aspirin) and with the chromophore of GFP and other fluorescent proteins, and noted that an n?p* interaction could have directed the prebiotic genesis of ribonucleotides.

<i>n</i>→<i>π</i>* Interactions in proteins and small molecules

245th National Meeting (2013)

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n→π* Interactions in proteins and small molecules