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 language | English (US) |
|---|---|
| Pages (from-to) | 352-355 |
| Number of pages | 4 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 458 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 2 2015 |
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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
At least 10% shorter C-H bonds in cryogenic protein crystal structures than in current AMBER forcefields. / Pang, Yuan-Ping.
In: Biochemical and Biophysical Research Communications, Vol. 458, No. 2, 02.03.2015, p. 352-355.Research output: Contribution to journal › Article
}
TY - JOUR
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.
KW - Bond parameters
KW - Chignolin
KW - Cryogenic crystal structures
KW - Force field
KW - Protein folding
KW - β-Hairpin
UR - http://www.scopus.com/inward/record.url?scp=84923295175&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84923295175&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2015.01.115
DO - 10.1016/j.bbrc.2015.01.115
M3 - Article
C2 - 25661001
AN - SCOPUS:84923295175
VL - 458
SP - 352
EP - 355
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -