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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.


Dibutyl ether guided toward an open or a closed conformation basedon calculated X-ray scattering. (A) Example conformations from anunrestrained simulation, with various end-to-end distances in Å,chosen at random for each distance. (B, C) Distance distributionsof an unrestrained simulation (black) and of XS-guided MD simulationsaiming at an open conformation (panel (B), 9.8 Å) and a closedconformation (panel (C), 5.0 Å) with kχ values as indicated (blue). Insets show average calculated scatteringprofiles for each kχ, as a differencerelative to the open conformation. There, red curves correspond todifferent kχ values, while targetcurves are shown in black.
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fig1: Dibutyl ether guided toward an open or a closed conformation basedon calculated X-ray scattering. (A) Example conformations from anunrestrained simulation, with various end-to-end distances in Å,chosen at random for each distance. (B, C) Distance distributionsof an unrestrained simulation (black) and of XS-guided MD simulationsaiming at an open conformation (panel (B), 9.8 Å) and a closedconformation (panel (C), 5.0 Å) with kχ values as indicated (blue). Insets show average calculated scatteringprofiles for each kχ, as a differencerelative to the open conformation. There, red curves correspond todifferent kχ values, while targetcurves are shown in black.

Mentions: The linear dibutylether molecule was first simulated without experimental constraintsunder vacuum for 10 ns, and the degree of openness of the carbon–oxygenchain considered. Figure 1A shows examplesof the conformations encountered, and the distribution of end-to-enddistances (RC1–C8) is shown inFigures 1B and 1C (blackcurve).


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)

Dibutyl ether guided toward an open or a closed conformation basedon calculated X-ray scattering. (A) Example conformations from anunrestrained simulation, with various end-to-end distances in Å,chosen at random for each distance. (B, C) Distance distributionsof an unrestrained simulation (black) and of XS-guided MD simulationsaiming at an open conformation (panel (B), 9.8 Å) and a closedconformation (panel (C), 5.0 Å) with kχ values as indicated (blue). Insets show average calculated scatteringprofiles for each kχ, as a differencerelative to the open conformation. There, red curves correspond todifferent kχ values, while targetcurves are shown in black.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Dibutyl ether guided toward an open or a closed conformation basedon calculated X-ray scattering. (A) Example conformations from anunrestrained simulation, with various end-to-end distances in Å,chosen at random for each distance. (B, C) Distance distributionsof an unrestrained simulation (black) and of XS-guided MD simulationsaiming at an open conformation (panel (B), 9.8 Å) and a closedconformation (panel (C), 5.0 Å) with kχ values as indicated (blue). Insets show average calculated scatteringprofiles for each kχ, as a differencerelative to the open conformation. There, red curves correspond todifferent kχ values, while targetcurves are shown in black.
Mentions: The linear dibutylether molecule was first simulated without experimental constraintsunder vacuum for 10 ns, and the degree of openness of the carbon–oxygenchain considered. Figure 1A shows examplesof the conformations encountered, and the distribution of end-to-enddistances (RC1–C8) is shown inFigures 1B and 1C (blackcurve).

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.