Limits...
High-resolution crystal structures of protein helices reconciled with three-centered hydrogen bonds and multipole electrostatics.

Kuster DJ, Liu C, Fang Z, Ponder JW, Marshall GR - PLoS ONE (2015)

Bottom Line: The reason why they have been overlooked by structural biologists depends on the small crankshaft-like changes in orientation of the amide bond that allows maintenance of the overall helical parameters (helix pitch (p) and residues per turn (n)).The Pauling 3.6(13) α-helix fits the high-resolution experimental data with the minor exception of the amide-carbonyl electron density, but the previously associated backbone torsional angles (Φ, Ψ) needed slight modification to be reconciled with three-atom centered H-bonds and multipole electrostatics.Thus, a new standard helix, the 3.6(13/10)-, Némethy- or N-helix, is proposed.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Washington University, St. Louis, MO, United States of America.

ABSTRACT
Theoretical and experimental evidence for non-linear hydrogen bonds in protein helices is ubiquitous. In particular, amide three-centered hydrogen bonds are common features of helices in high-resolution crystal structures of proteins. These high-resolution structures (1.0 to 1.5 Å nominal crystallographic resolution) position backbone atoms without significant bias from modeling constraints and identify Φ = -62°, ψ = -43 as the consensus backbone torsional angles of protein helices. These torsional angles preserve the atomic positions of α-β carbons of the classic Pauling α-helix while allowing the amide carbonyls to form bifurcated hydrogen bonds as first suggested by Némethy et al. in 1967. Molecular dynamics simulations of a capped 12-residue oligoalanine in water with AMOEBA (Atomic Multipole Optimized Energetics for Biomolecular Applications), a second-generation force field that includes multipole electrostatics and polarizability, reproduces the experimentally observed high-resolution helical conformation and correctly reorients the amide-bond carbonyls into bifurcated hydrogen bonds. This simple modification of backbone torsional angles reconciles experimental and theoretical views to provide a unified view of amide three-centered hydrogen bonds as crucial components of protein helices. The reason why they have been overlooked by structural biologists depends on the small crankshaft-like changes in orientation of the amide bond that allows maintenance of the overall helical parameters (helix pitch (p) and residues per turn (n)). The Pauling 3.6(13) α-helix fits the high-resolution experimental data with the minor exception of the amide-carbonyl electron density, but the previously associated backbone torsional angles (Φ, Ψ) needed slight modification to be reconciled with three-atom centered H-bonds and multipole electrostatics. Thus, a new standard helix, the 3.6(13/10)-, Némethy- or N-helix, is proposed. Due to the use of constraints from monopole force fields and assumed secondary structures used in low-resolution refinement of electron density of proteins, such structures in the PDB often show linear hydrogen bonding.

Show MeSH

Related in: MedlinePlus

Hydrogen-bonding alternatives; linear H-bond assumed by the Pauling/Donohue groups; three-centered hydrogen bonds to carbonyl oxygens that dominate crystal structures of small organic molecules [6].
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4403875&req=5

pone.0123146.g001: Hydrogen-bonding alternatives; linear H-bond assumed by the Pauling/Donohue groups; three-centered hydrogen bonds to carbonyl oxygens that dominate crystal structures of small organic molecules [6].

Mentions: The α-helix model is the result of powerful deductions about the chemistry of amide bonds and peptides by Pauling [1]. First, amide bonds were planar due to resonance, a fact not appreciated by others in the field (see Eisenberg [2]); second, intramolecular hydrogen bonding needed to be optimized; and third, there was no reason to restrict a model to an integral number of residues per turn. In 1951, Pauling, Corey and Branson [1] applied these constraints in the context of regular protein sequences to yield the α-helix, which originally had 3.7 residues-per-turn [3] and 13 atoms in a hydrogen-bonded ring (i.e., α-helix = 3.713-helix). Two critical assumptions were: the concept of linear groups (i.e., a series of residues all having identical conformations), and the use of single, linear hydrogen bonds (Fig 1) to fold the sequence in space by imposing a distance constraint between two non-consecutive amino acids in space. In one of the subsequent nine papers Pauling and Corey published in 1951, they suggested, “The number of residues per turn is fixed primarily by the bond angle at the α carbon atom; it varies from 3.60 for bond angle 108.9° to 3.67 for bond angle 110.8°”. The backbone torsional angles (Φ = -57°, Ψ = -47°) associated with the α-helix (3.613-helix) became official in the article by the IUPAC-IUB Commission on Biochemical Nomenclature published in 1970 [4]. These values were based on experimental fitting of parameters to diffraction data for poly-L-alanine in 1967 by Arnott and Dover [5].


High-resolution crystal structures of protein helices reconciled with three-centered hydrogen bonds and multipole electrostatics.

Kuster DJ, Liu C, Fang Z, Ponder JW, Marshall GR - PLoS ONE (2015)

Hydrogen-bonding alternatives; linear H-bond assumed by the Pauling/Donohue groups; three-centered hydrogen bonds to carbonyl oxygens that dominate crystal structures of small organic molecules [6].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4403875&req=5

pone.0123146.g001: Hydrogen-bonding alternatives; linear H-bond assumed by the Pauling/Donohue groups; three-centered hydrogen bonds to carbonyl oxygens that dominate crystal structures of small organic molecules [6].
Mentions: The α-helix model is the result of powerful deductions about the chemistry of amide bonds and peptides by Pauling [1]. First, amide bonds were planar due to resonance, a fact not appreciated by others in the field (see Eisenberg [2]); second, intramolecular hydrogen bonding needed to be optimized; and third, there was no reason to restrict a model to an integral number of residues per turn. In 1951, Pauling, Corey and Branson [1] applied these constraints in the context of regular protein sequences to yield the α-helix, which originally had 3.7 residues-per-turn [3] and 13 atoms in a hydrogen-bonded ring (i.e., α-helix = 3.713-helix). Two critical assumptions were: the concept of linear groups (i.e., a series of residues all having identical conformations), and the use of single, linear hydrogen bonds (Fig 1) to fold the sequence in space by imposing a distance constraint between two non-consecutive amino acids in space. In one of the subsequent nine papers Pauling and Corey published in 1951, they suggested, “The number of residues per turn is fixed primarily by the bond angle at the α carbon atom; it varies from 3.60 for bond angle 108.9° to 3.67 for bond angle 110.8°”. The backbone torsional angles (Φ = -57°, Ψ = -47°) associated with the α-helix (3.613-helix) became official in the article by the IUPAC-IUB Commission on Biochemical Nomenclature published in 1970 [4]. These values were based on experimental fitting of parameters to diffraction data for poly-L-alanine in 1967 by Arnott and Dover [5].

Bottom Line: The reason why they have been overlooked by structural biologists depends on the small crankshaft-like changes in orientation of the amide bond that allows maintenance of the overall helical parameters (helix pitch (p) and residues per turn (n)).The Pauling 3.6(13) α-helix fits the high-resolution experimental data with the minor exception of the amide-carbonyl electron density, but the previously associated backbone torsional angles (Φ, Ψ) needed slight modification to be reconciled with three-atom centered H-bonds and multipole electrostatics.Thus, a new standard helix, the 3.6(13/10)-, Némethy- or N-helix, is proposed.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Washington University, St. Louis, MO, United States of America.

ABSTRACT
Theoretical and experimental evidence for non-linear hydrogen bonds in protein helices is ubiquitous. In particular, amide three-centered hydrogen bonds are common features of helices in high-resolution crystal structures of proteins. These high-resolution structures (1.0 to 1.5 Å nominal crystallographic resolution) position backbone atoms without significant bias from modeling constraints and identify Φ = -62°, ψ = -43 as the consensus backbone torsional angles of protein helices. These torsional angles preserve the atomic positions of α-β carbons of the classic Pauling α-helix while allowing the amide carbonyls to form bifurcated hydrogen bonds as first suggested by Némethy et al. in 1967. Molecular dynamics simulations of a capped 12-residue oligoalanine in water with AMOEBA (Atomic Multipole Optimized Energetics for Biomolecular Applications), a second-generation force field that includes multipole electrostatics and polarizability, reproduces the experimentally observed high-resolution helical conformation and correctly reorients the amide-bond carbonyls into bifurcated hydrogen bonds. This simple modification of backbone torsional angles reconciles experimental and theoretical views to provide a unified view of amide three-centered hydrogen bonds as crucial components of protein helices. The reason why they have been overlooked by structural biologists depends on the small crankshaft-like changes in orientation of the amide bond that allows maintenance of the overall helical parameters (helix pitch (p) and residues per turn (n)). The Pauling 3.6(13) α-helix fits the high-resolution experimental data with the minor exception of the amide-carbonyl electron density, but the previously associated backbone torsional angles (Φ, Ψ) needed slight modification to be reconciled with three-atom centered H-bonds and multipole electrostatics. Thus, a new standard helix, the 3.6(13/10)-, Némethy- or N-helix, is proposed. Due to the use of constraints from monopole force fields and assumed secondary structures used in low-resolution refinement of electron density of proteins, such structures in the PDB often show linear hydrogen bonding.

Show MeSH
Related in: MedlinePlus