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n-->pi* interactions in proteins.

Bartlett GJ, Choudhary A, Raines RT, Woolfson DN - Nat. Chem. Biol. (2010)

Bottom Line: Natural bond orbital analysis predicted significant n-->pi* interactions in certain regions of the Ramachandran plot.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.

View Article: PubMed Central - PubMed

Affiliation: School of Chemistry, University of Bristol, Bristol, United Kingdom.

ABSTRACT
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.

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Kinship of hydrogen bonds and n→π* interactions in an α-helixa, s-rich lone-pair of an amide oxygen. b, p-rich lone-pair of an amide oxygen. c, ns→σ*: hydrogen bond in an α-helix. d, np→π*: n→π* interaction in an α-helix.
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Figure 1: Kinship of hydrogen bonds and n→π* interactions in an α-helixa, s-rich lone-pair of an amide oxygen. b, p-rich lone-pair of an amide oxygen. c, ns→σ*: hydrogen bond in an α-helix. d, np→π*: n→π* interaction in an α-helix.

Mentions: The extent of overlap between donor and acceptor orbitals is governed by their relative spatial orientation. Contrary to the expectations of valence shell electron pair repulsion (VSEPR) theory, the two lone pairs of divalent oxygen do not occupy equivalent orbitals6 that resemble “rabbit ears”7,8. For example, the lone pairs of a carbonyl oxygen are not in sp2 hybrid orbitals, but reside in non-degenerate s-rich and p-rich orbitals. The s-rich lone pair (ns) has ~60% s- and 40% p-character; whereas the p-rich lone pair (np) has ~100% p-character. In an amide oxygen, ns is aligned with the σ bond of the carbonyl group (Fig. 1a), and np is orthogonal to the π bond of that group (Fig. 1b).


n-->pi* interactions in proteins.

Bartlett GJ, Choudhary A, Raines RT, Woolfson DN - Nat. Chem. Biol. (2010)

Kinship of hydrogen bonds and n→π* interactions in an α-helixa, s-rich lone-pair of an amide oxygen. b, p-rich lone-pair of an amide oxygen. c, ns→σ*: hydrogen bond in an α-helix. d, np→π*: n→π* interaction in an α-helix.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2921280&req=5

Figure 1: Kinship of hydrogen bonds and n→π* interactions in an α-helixa, s-rich lone-pair of an amide oxygen. b, p-rich lone-pair of an amide oxygen. c, ns→σ*: hydrogen bond in an α-helix. d, np→π*: n→π* interaction in an α-helix.
Mentions: The extent of overlap between donor and acceptor orbitals is governed by their relative spatial orientation. Contrary to the expectations of valence shell electron pair repulsion (VSEPR) theory, the two lone pairs of divalent oxygen do not occupy equivalent orbitals6 that resemble “rabbit ears”7,8. For example, the lone pairs of a carbonyl oxygen are not in sp2 hybrid orbitals, but reside in non-degenerate s-rich and p-rich orbitals. The s-rich lone pair (ns) has ~60% s- and 40% p-character; whereas the p-rich lone pair (np) has ~100% p-character. In an amide oxygen, ns is aligned with the σ bond of the carbonyl group (Fig. 1a), and np is orthogonal to the π bond of that group (Fig. 1b).

Bottom Line: Natural bond orbital analysis predicted significant n-->pi* interactions in certain regions of the Ramachandran plot.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.

View Article: PubMed Central - PubMed

Affiliation: School of Chemistry, University of Bristol, Bristol, United Kingdom.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus