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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.


Method validation against the D. radiodurans bacterial phytochrome. (A) The center-of-mass distances betweenthe globular PHY domains (residues 330–445 and 480–503)on opposing monomers, as well as the evolution of the scattering energyterm; the initial scattering energy was 300 kJ/mol. (B) Theoreticaldifference scattering during the second half of the 4 ns run. (C)Structural views of the Pr and Pfr solution structures,10 and a trajectory view over the second half ofthe run, superimposed on the Pfr target structure.
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fig3: Method validation against the D. radiodurans bacterial phytochrome. (A) The center-of-mass distances betweenthe globular PHY domains (residues 330–445 and 480–503)on opposing monomers, as well as the evolution of the scattering energyterm; the initial scattering energy was 300 kJ/mol. (B) Theoreticaldifference scattering during the second half of the 4 ns run. (C)Structural views of the Pr and Pfr solution structures,10 and a trajectory view over the second half ofthe run, superimposed on the Pfr target structure.

Mentions: Figure 3A showsthat guiding the simulationtoward experimental scattering data causes the distance between thephytochrome dimer’s opposing PHY domains to grow.51 As the PHY–PHY distance approaches thevalue previously found,10 the global conformationof the dimer reproduces the Pfr solution structure. Indeed, the structuraloverlap shown in Figure 3C illustrates thatthese structures are identical at the low-resolution level. Thus,XS-guided MD simulations are capable of refining solution structuresbased on an initial model and experimental X-ray difference scatteringdata.


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)

Method validation against the D. radiodurans bacterial phytochrome. (A) The center-of-mass distances betweenthe globular PHY domains (residues 330–445 and 480–503)on opposing monomers, as well as the evolution of the scattering energyterm; the initial scattering energy was 300 kJ/mol. (B) Theoreticaldifference scattering during the second half of the 4 ns run. (C)Structural views of the Pr and Pfr solution structures,10 and a trajectory view over the second half ofthe run, superimposed on the Pfr target structure.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Method validation against the D. radiodurans bacterial phytochrome. (A) The center-of-mass distances betweenthe globular PHY domains (residues 330–445 and 480–503)on opposing monomers, as well as the evolution of the scattering energyterm; the initial scattering energy was 300 kJ/mol. (B) Theoreticaldifference scattering during the second half of the 4 ns run. (C)Structural views of the Pr and Pfr solution structures,10 and a trajectory view over the second half ofthe run, superimposed on the Pfr target structure.
Mentions: Figure 3A showsthat guiding the simulationtoward experimental scattering data causes the distance between thephytochrome dimer’s opposing PHY domains to grow.51 As the PHY–PHY distance approaches thevalue previously found,10 the global conformationof the dimer reproduces the Pfr solution structure. Indeed, the structuraloverlap shown in Figure 3C illustrates thatthese structures are identical at the low-resolution level. Thus,XS-guided MD simulations are capable of refining solution structuresbased on an initial model and experimental X-ray difference scatteringdata.

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.