期刊
PLOS ONE
卷 10, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0123146
关键词
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资金
- National Institutes of Health (NIH) [R01-GM068460]
- Department of Defense [HDTRA1-09-CHEM-BIO-BAA]
- Ewing Marion Kauffman Foundation
- Department of Biomedical Engineering at Washington University
- NSF [CHE-0535675]
- NIH [R01-GM6955302]
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 angstrom nominal crystallographic resolution) position backbone atoms without significant bias from modeling constraints and identify Phi = -62 degrees, Psi = -43 as the consensus backbone torsional angles of protein helices. These torsional angles preserve the atomic positions of alpha-beta carbons of the classic Pauling alpha-helix while allowing the amide carbonyls to form bifurcated hydrogen bonds as first suggested by Nemethy 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) alpha-helix fits the high-resolution experimental data with the minor exception of the amide-carbonyl electron density, but the previously associated backbone torsional angles (Phi, Psi) 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)-, Nemethy- 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.
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