At least 10% shorter C-H bonds in cryogenic protein crystal structures than in current AMBER forcefields

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Abstract

High resolution protein crystal structures resolved with X-ray diffraction data at cryogenic temperature are commonly used as experimental data to refine forcefields and evaluate protein folding simulations. However, it has been unclear hitherto whether the C-H bond lengths in cryogenic protein structures are significantly different from those defined in forcefields to affect protein folding simulations. This article reports the finding that the C-H bonds in high resolution cryogenic protein structures are 10-14% shorter than those defined in current AMBER forcefields, according to 3709 C-H bonds in the cryogenic protein structures with resolutions of 0.62-0.79 Å. Also, 20 all-atom, isothermal-isobaric, 0.5-μs molecular dynamics simulations showed that chignolin folded from a fully-extended backbone formation to the native β-hairpin conformation in the simulations using AMBER forcefield FF12SB at 300 K with an aggregated native state population including standard error of 10 ± 4%. However, the aggregated native state population with standard error reduced to 3 ± 2% in the same simulations except that C-H bonds were shortened by 10-14%. Furthermore, the aggregated native state populations with standard errors increased to 35 ± 3% and 26 ± 3% when using FF12MC, which is based on AMBER forcefield FF99, with and without the shortened C-H bonds, respectively. These results show that the 10-14% bond length differences can significantly affect protein folding simulations and suggest that re-parameterization of C-H bonds according to the cryogenic structures could improve the ability of a forcefield to fold proteins in molecular dynamics simulations.

Original languageEnglish (US)
Pages (from-to)352-355
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume458
Issue number2
DOIs
StatePublished - Mar 2 2015

Fingerprint

Cryogenics
Protein folding
Crystal structure
Protein Folding
Bond length
Molecular Dynamics Simulation
Proteins
Molecular dynamics
Population
Computer simulation
Parameterization
X-Ray Diffraction
Conformations
X ray diffraction
Atoms
Temperature

Keywords

  • Bond parameters
  • Chignolin
  • Cryogenic crystal structures
  • Force field
  • Protein folding
  • β-Hairpin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

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title = "At least 10{\%} shorter C-H bonds in cryogenic protein crystal structures than in current AMBER forcefields",
abstract = "High resolution protein crystal structures resolved with X-ray diffraction data at cryogenic temperature are commonly used as experimental data to refine forcefields and evaluate protein folding simulations. However, it has been unclear hitherto whether the C-H bond lengths in cryogenic protein structures are significantly different from those defined in forcefields to affect protein folding simulations. This article reports the finding that the C-H bonds in high resolution cryogenic protein structures are 10-14{\%} shorter than those defined in current AMBER forcefields, according to 3709 C-H bonds in the cryogenic protein structures with resolutions of 0.62-0.79 {\AA}. Also, 20 all-atom, isothermal-isobaric, 0.5-μs molecular dynamics simulations showed that chignolin folded from a fully-extended backbone formation to the native β-hairpin conformation in the simulations using AMBER forcefield FF12SB at 300 K with an aggregated native state population including standard error of 10 ± 4{\%}. However, the aggregated native state population with standard error reduced to 3 ± 2{\%} in the same simulations except that C-H bonds were shortened by 10-14{\%}. Furthermore, the aggregated native state populations with standard errors increased to 35 ± 3{\%} and 26 ± 3{\%} when using FF12MC, which is based on AMBER forcefield FF99, with and without the shortened C-H bonds, respectively. These results show that the 10-14{\%} bond length differences can significantly affect protein folding simulations and suggest that re-parameterization of C-H bonds according to the cryogenic structures could improve the ability of a forcefield to fold proteins in molecular dynamics simulations.",
keywords = "Bond parameters, Chignolin, Cryogenic crystal structures, Force field, Protein folding, β-Hairpin",
author = "Yuan-Ping Pang",
year = "2015",
month = "3",
day = "2",
doi = "10.1016/j.bbrc.2015.01.115",
language = "English (US)",
volume = "458",
pages = "352--355",
journal = "Biochemical and Biophysical Research Communications",
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T1 - At least 10% shorter C-H bonds in cryogenic protein crystal structures than in current AMBER forcefields

AU - Pang, Yuan-Ping

PY - 2015/3/2

Y1 - 2015/3/2

N2 - High resolution protein crystal structures resolved with X-ray diffraction data at cryogenic temperature are commonly used as experimental data to refine forcefields and evaluate protein folding simulations. However, it has been unclear hitherto whether the C-H bond lengths in cryogenic protein structures are significantly different from those defined in forcefields to affect protein folding simulations. This article reports the finding that the C-H bonds in high resolution cryogenic protein structures are 10-14% shorter than those defined in current AMBER forcefields, according to 3709 C-H bonds in the cryogenic protein structures with resolutions of 0.62-0.79 Å. Also, 20 all-atom, isothermal-isobaric, 0.5-μs molecular dynamics simulations showed that chignolin folded from a fully-extended backbone formation to the native β-hairpin conformation in the simulations using AMBER forcefield FF12SB at 300 K with an aggregated native state population including standard error of 10 ± 4%. However, the aggregated native state population with standard error reduced to 3 ± 2% in the same simulations except that C-H bonds were shortened by 10-14%. Furthermore, the aggregated native state populations with standard errors increased to 35 ± 3% and 26 ± 3% when using FF12MC, which is based on AMBER forcefield FF99, with and without the shortened C-H bonds, respectively. These results show that the 10-14% bond length differences can significantly affect protein folding simulations and suggest that re-parameterization of C-H bonds according to the cryogenic structures could improve the ability of a forcefield to fold proteins in molecular dynamics simulations.

AB - High resolution protein crystal structures resolved with X-ray diffraction data at cryogenic temperature are commonly used as experimental data to refine forcefields and evaluate protein folding simulations. However, it has been unclear hitherto whether the C-H bond lengths in cryogenic protein structures are significantly different from those defined in forcefields to affect protein folding simulations. This article reports the finding that the C-H bonds in high resolution cryogenic protein structures are 10-14% shorter than those defined in current AMBER forcefields, according to 3709 C-H bonds in the cryogenic protein structures with resolutions of 0.62-0.79 Å. Also, 20 all-atom, isothermal-isobaric, 0.5-μs molecular dynamics simulations showed that chignolin folded from a fully-extended backbone formation to the native β-hairpin conformation in the simulations using AMBER forcefield FF12SB at 300 K with an aggregated native state population including standard error of 10 ± 4%. However, the aggregated native state population with standard error reduced to 3 ± 2% in the same simulations except that C-H bonds were shortened by 10-14%. Furthermore, the aggregated native state populations with standard errors increased to 35 ± 3% and 26 ± 3% when using FF12MC, which is based on AMBER forcefield FF99, with and without the shortened C-H bonds, respectively. These results show that the 10-14% bond length differences can significantly affect protein folding simulations and suggest that re-parameterization of C-H bonds according to the cryogenic structures could improve the ability of a forcefield to fold proteins in molecular dynamics simulations.

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KW - Cryogenic crystal structures

KW - Force field

KW - Protein folding

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