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Deciphering Solution Scattering Data with Experimentally Guided Molecular Dynamics Simulations.

Björling A, Niebling S, Marcellini M, van der Spoel D, Westenhoff S - J Chem Theory Comput (2015)

Bottom Line: Extracting structural information from the resulting difference X-ray scattering data is a daunting task.Therefore, the energy landscape is biased toward conformations that agree with experimental data.We describe and verify the method, and we provide an implementation in GROMACS.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg , SE-405 30 Gothenburg, Sweden.

ABSTRACT

Time-resolved X-ray solution scattering is an increasingly popular method to measure conformational changes in proteins. Extracting structural information from the resulting difference X-ray scattering data is a daunting task. We present a method in which the limited but precious information encoded in such scattering curves is combined with the chemical knowledge of molecular force fields. The molecule of interest is then refined toward experimental data using molecular dynamics simulation. Therefore, the energy landscape is biased toward conformations that agree with experimental data. We describe and verify the method, and we provide an implementation in GROMACS.

No MeSH data available.


Magnitude and position of the ΔS peak at q ≅ 1/nm for various PHY−PHYdistances. Thedata are taken from the trajectories presented by Takala etal.10
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fig4: Magnitude and position of the ΔS peak at q ≅ 1/nm for various PHY−PHYdistances. Thedata are taken from the trajectories presented by Takala etal.10

Mentions: We note that, while the application to phytochromephotoconversionvalidates the XS-guided MD method as such, and it lends confidenceto the nature of the previously proposed structural change,10 the magnitude of the opening between the PHYdomains cannot be rigorously defined at very large openings. Thiswas already recognized in ref (10) and does not affect the conlusions drawn in that paper;however, it does illustrate a potential problem in refinement againstdifference X-ray solution scattering data. The parameter α,which describes the experimental conversion efficiency and is neededfor the correct scaling of calculated to experimental data, was estimatedbased on the original analysis, where α was arbitrarily scaledfor best fit to data.10 In fact, the absolutesize of the difference signal, and therefore the precise value ofα, affects the degree to which the phytochrome dimer opens upin XS-guided MD refinement. This is illustrated in Figure 4, which shows predicted peak positions for differencescattering curves based on the previously published trajectories.10 As the dimer opening increases, the peak firstshifts along the q-axis, and then, after an initialopening to ∼5.5 nm, instead grows in magnitude. Thus, experimentaldetermination of the yield parameter α is important for successfulstructural refinement.


Deciphering Solution Scattering Data with Experimentally Guided Molecular Dynamics Simulations.

Björling A, Niebling S, Marcellini M, van der Spoel D, Westenhoff S - J Chem Theory Comput (2015)

Magnitude and position of the ΔS peak at q ≅ 1/nm for various PHY−PHYdistances. Thedata are taken from the trajectories presented by Takala etal.10
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325560&req=5

fig4: Magnitude and position of the ΔS peak at q ≅ 1/nm for various PHY−PHYdistances. Thedata are taken from the trajectories presented by Takala etal.10
Mentions: We note that, while the application to phytochromephotoconversionvalidates the XS-guided MD method as such, and it lends confidenceto the nature of the previously proposed structural change,10 the magnitude of the opening between the PHYdomains cannot be rigorously defined at very large openings. Thiswas already recognized in ref (10) and does not affect the conlusions drawn in that paper;however, it does illustrate a potential problem in refinement againstdifference X-ray solution scattering data. The parameter α,which describes the experimental conversion efficiency and is neededfor the correct scaling of calculated to experimental data, was estimatedbased on the original analysis, where α was arbitrarily scaledfor best fit to data.10 In fact, the absolutesize of the difference signal, and therefore the precise value ofα, affects the degree to which the phytochrome dimer opens upin XS-guided MD refinement. This is illustrated in Figure 4, which shows predicted peak positions for differencescattering curves based on the previously published trajectories.10 As the dimer opening increases, the peak firstshifts along the q-axis, and then, after an initialopening to ∼5.5 nm, instead grows in magnitude. Thus, experimentaldetermination of the yield parameter α is important for successfulstructural refinement.

Bottom Line: Extracting structural information from the resulting difference X-ray scattering data is a daunting task.Therefore, the energy landscape is biased toward conformations that agree with experimental data.We describe and verify the method, and we provide an implementation in GROMACS.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg , SE-405 30 Gothenburg, Sweden.

ABSTRACT

Time-resolved X-ray solution scattering is an increasingly popular method to measure conformational changes in proteins. Extracting structural information from the resulting difference X-ray scattering data is a daunting task. We present a method in which the limited but precious information encoded in such scattering curves is combined with the chemical knowledge of molecular force fields. The molecule of interest is then refined toward experimental data using molecular dynamics simulation. Therefore, the energy landscape is biased toward conformations that agree with experimental data. We describe and verify the method, and we provide an implementation in GROMACS.

No MeSH data available.