Abstract
A sample of 35 independent molecular dynamics (MD) simulations of calmodulin (CaM) equilibrium dynamics was prepared from different but equally plausible initial conditions (20 simulations of the wild-type protein and 15 simulations of the D129N mutant). CaM's radius of gyration and backbone mean-square fluctuations were analyzed for the effect of the D129N mutation, and simulations were compared with experiments. Statistical tests were employed for quantitative comparisons at the desired error level. The computational model predicted statistically significant compaction of CaM relative to the crystal structure, consistent with the results of small-angle X-ray scattering (SAXS) experiments. This effect was not observed in several previously reported studies of (Ca2+)4-CaM, which relied on a single MD run. In contrast to radius of gyration, backbone mean-square fluctuations showed a distinctly non-normal and positively skewed distribution for nearly all residues. Furthermore, the D129N mutation affected the backbone dynamics in a complex manner and reduced the mobility of Glu123, Met124, Ile125, Arg126, and Glu127 located in the adjacent α-helix G. The implications of these observations for the comparisons of MD simulations with experiments are discussed. The proposed approach may be useful in studies of protein equilibrium dynamics where MD simulations fall short of properly sampling the conformational space, and when the comparison with experiments is affected by the reproducibility of the computational model. Published by Cold Spring Harbor Laboratory Press.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2955-2963 |
| Number of pages | 9 |
| Journal | Protein Science |
| Volume | 14 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2005 |
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Keywords
- Accuracy
- Calmodulin
- MD simulations
- Precision
- Protein dynamics
- Reproducibility
ASJC Scopus subject areas
- Biochemistry
Cite this
A statistical approach to the interpretation of molecular dynamics simulations of calmodulin equilibrium dynamics. / Likić, Vladimir A.; Gooley, Paul R.; Speed, Terence P.; Strehler, Emanuel E.
In: Protein Science, Vol. 14, No. 12, 12.2005, p. 2955-2963.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A statistical approach to the interpretation of molecular dynamics simulations of calmodulin equilibrium dynamics
AU - Likić, Vladimir A.
AU - Gooley, Paul R.
AU - Speed, Terence P.
AU - Strehler, Emanuel E.
PY - 2005/12
Y1 - 2005/12
N2 - A sample of 35 independent molecular dynamics (MD) simulations of calmodulin (CaM) equilibrium dynamics was prepared from different but equally plausible initial conditions (20 simulations of the wild-type protein and 15 simulations of the D129N mutant). CaM's radius of gyration and backbone mean-square fluctuations were analyzed for the effect of the D129N mutation, and simulations were compared with experiments. Statistical tests were employed for quantitative comparisons at the desired error level. The computational model predicted statistically significant compaction of CaM relative to the crystal structure, consistent with the results of small-angle X-ray scattering (SAXS) experiments. This effect was not observed in several previously reported studies of (Ca2+)4-CaM, which relied on a single MD run. In contrast to radius of gyration, backbone mean-square fluctuations showed a distinctly non-normal and positively skewed distribution for nearly all residues. Furthermore, the D129N mutation affected the backbone dynamics in a complex manner and reduced the mobility of Glu123, Met124, Ile125, Arg126, and Glu127 located in the adjacent α-helix G. The implications of these observations for the comparisons of MD simulations with experiments are discussed. The proposed approach may be useful in studies of protein equilibrium dynamics where MD simulations fall short of properly sampling the conformational space, and when the comparison with experiments is affected by the reproducibility of the computational model. Published by Cold Spring Harbor Laboratory Press.
AB - A sample of 35 independent molecular dynamics (MD) simulations of calmodulin (CaM) equilibrium dynamics was prepared from different but equally plausible initial conditions (20 simulations of the wild-type protein and 15 simulations of the D129N mutant). CaM's radius of gyration and backbone mean-square fluctuations were analyzed for the effect of the D129N mutation, and simulations were compared with experiments. Statistical tests were employed for quantitative comparisons at the desired error level. The computational model predicted statistically significant compaction of CaM relative to the crystal structure, consistent with the results of small-angle X-ray scattering (SAXS) experiments. This effect was not observed in several previously reported studies of (Ca2+)4-CaM, which relied on a single MD run. In contrast to radius of gyration, backbone mean-square fluctuations showed a distinctly non-normal and positively skewed distribution for nearly all residues. Furthermore, the D129N mutation affected the backbone dynamics in a complex manner and reduced the mobility of Glu123, Met124, Ile125, Arg126, and Glu127 located in the adjacent α-helix G. The implications of these observations for the comparisons of MD simulations with experiments are discussed. The proposed approach may be useful in studies of protein equilibrium dynamics where MD simulations fall short of properly sampling the conformational space, and when the comparison with experiments is affected by the reproducibility of the computational model. Published by Cold Spring Harbor Laboratory Press.
KW - Accuracy
KW - Calmodulin
KW - MD simulations
KW - Precision
KW - Protein dynamics
KW - Reproducibility
UR - http://www.scopus.com/inward/record.url?scp=28844490605&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=28844490605&partnerID=8YFLogxK
U2 - 10.1110/ps.051681605
DO - 10.1110/ps.051681605
M3 - Article
C2 - 16322577
AN - SCOPUS:28844490605
VL - 14
SP - 2955
EP - 2963
JO - Protein Science
JF - Protein Science
SN - 0961-8368
IS - 12
ER -