title: High-resolution crystal structures of protein helices reconciled with three-centered hydrogen bonds and multipole electrostatics.
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.
authors.affiliation: Department of Biomedical Engineering, Washington University, St. Louis, MO, United States of America.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kuster
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO, United States of America.
authors.forename: Chengyu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Biomedical Engineering, Washington University, St. Louis, MO, United States of America.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO, United States of America.
authors.forename: Jay W
authors.initials: JW
authors.lastname: Ponder
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Washington University, St. Louis, MO, United States of America.
authors.forename: Garland R
authors.initials: GR
authors.lastname: Marshall
mesh_terms: D018360:Crystallography, X-Ray; D030562:Databases, Protein; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D033363:Neutron Diffraction; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D011789:Quantum Theory; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D011506:Proteins