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

Contours and 3D surface helical pitch (n d) overlaid on 2D φ, ψ plot.Positions of classic α-helix (φ = −57, ψ = −47), 310-helix (φ = −49, ψ = −26), and experimental Némethy-, N- or 3.613/10-helix (φ = −62, ψ = −43) are indicated. Note that the helical pitch is nearly identical for the α- and 3.613/10-helices—they lie on a contour of essentially equal value.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123146.g008: Contours and 3D surface helical pitch (n d) overlaid on 2D φ, ψ plot.Positions of classic α-helix (φ = −57, ψ = −47), 310-helix (φ = −49, ψ = −26), and experimental Némethy-, N- or 3.613/10-helix (φ = −62, ψ = −43) are indicated. Note that the helical pitch is nearly identical for the α- and 3.613/10-helices—they lie on a contour of essentially equal value.

Mentions: The mathematics used to analyze the impact of changes in backbone torsion angles on helix pitch and orientation of Cα-Cβ vectors in proteins was described by Ramachandran et al. [51]. A more recent and thorough generalization has been made based on quaternions [52]. The following equations were used to analyze the impact of the backbone torsion parameters Φ, Ψ on helix pitch (p) and residues per turn (n) (Figs 7, 8, 9 and 10):


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)

Contours and 3D surface helical pitch (n d) overlaid on 2D φ, ψ plot.Positions of classic α-helix (φ = −57, ψ = −47), 310-helix (φ = −49, ψ = −26), and experimental Némethy-, N- or 3.613/10-helix (φ = −62, ψ = −43) are indicated. Note that the helical pitch is nearly identical for the α- and 3.613/10-helices—they lie on a contour of essentially equal value.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123146.g008: Contours and 3D surface helical pitch (n d) overlaid on 2D φ, ψ plot.Positions of classic α-helix (φ = −57, ψ = −47), 310-helix (φ = −49, ψ = −26), and experimental Némethy-, N- or 3.613/10-helix (φ = −62, ψ = −43) are indicated. Note that the helical pitch is nearly identical for the α- and 3.613/10-helices—they lie on a contour of essentially equal value.
Mentions: The mathematics used to analyze the impact of changes in backbone torsion angles on helix pitch and orientation of Cα-Cβ vectors in proteins was described by Ramachandran et al. [51]. A more recent and thorough generalization has been made based on quaternions [52]. The following equations were used to analyze the impact of the backbone torsion parameters Φ, Ψ on helix pitch (p) and residues per turn (n) (Figs 7, 8, 9 and 10):

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