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Normal Mode Flexible Fitting of High-Resolution Structures of Biological Molecules Toward SAXS Data.

Gorba C, Tama F - Bioinform Biol Insights (2010)

Bottom Line: We present a method to reconstruct a three-dimensional protein structure from an atomic pair distribution function derived from the scattering intensity profile from SAXS data by flexibly fitting known x-ray structures.For computational efficiency, the protein and water molecules included in the protein first hydration shell are coarse-grained.Illustrative results of our flexible fitting studies on simulated SAXS data from five different proteins are presented.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, The University of Arizona, 1041 E. Lowell Street, Tucson, AZ, 85721.

ABSTRACT
We present a method to reconstruct a three-dimensional protein structure from an atomic pair distribution function derived from the scattering intensity profile from SAXS data by flexibly fitting known x-ray structures. This method uses a linear combination of low-frequency normal modes from an elastic network description of the molecule in an iterative manner to deform the structure to conform optimally to the target pair distribution function derived from SAXS data. For computational efficiency, the protein and water molecules included in the protein first hydration shell are coarse-grained. In this paper, we demonstrate the validity of our coarse-graining approach to study SAXS data. Illustrative results of our flexible fitting studies on simulated SAXS data from five different proteins are presented.

No MeSH data available.


Coarse-graining process and scaling for Adenylate Kinase. (a) Adenlynate Kinase surrounded with several layers of water molecules (colored in gray). Only water molecules shown in light blue are considered to estimate the Intensity Scattering profile and consequently derived the P(r). (b) P(r) for the Adenylate Kinase as obtained with eq. 1 or with the program suite Crysol/Gnom. Good agreement between the P(r) is observed. (c) Coarse-graining: adenylate kinase is shown as ribbon, only its Cα atoms are considered (not shown) and from the first shell of water molecules surrounding the protein (transparent gray), only 1/8 of these molecules are kept (light blue). (d) Simulated experimental data using all atom structures: P(r) for the open and close forms of the Adenylate Kinase as derived from the Crysol/Gnom program suite. (e) P(r) for the coarse-grained model of the protein/solvent system as calculated using eq. 1, Pini(r). The target Ptar(r) is prepared by scaling Pexp(r) so that its integral matches the integral of the coarse-grained model Pini(r). Note the good agreement between the scaled P(r) and the P(r) derived from all-atom structure is similar.
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f1-bbi-2010-043: Coarse-graining process and scaling for Adenylate Kinase. (a) Adenlynate Kinase surrounded with several layers of water molecules (colored in gray). Only water molecules shown in light blue are considered to estimate the Intensity Scattering profile and consequently derived the P(r). (b) P(r) for the Adenylate Kinase as obtained with eq. 1 or with the program suite Crysol/Gnom. Good agreement between the P(r) is observed. (c) Coarse-graining: adenylate kinase is shown as ribbon, only its Cα atoms are considered (not shown) and from the first shell of water molecules surrounding the protein (transparent gray), only 1/8 of these molecules are kept (light blue). (d) Simulated experimental data using all atom structures: P(r) for the open and close forms of the Adenylate Kinase as derived from the Crysol/Gnom program suite. (e) P(r) for the coarse-grained model of the protein/solvent system as calculated using eq. 1, Pini(r). The target Ptar(r) is prepared by scaling Pexp(r) so that its integral matches the integral of the coarse-grained model Pini(r). Note the good agreement between the scaled P(r) and the P(r) derived from all-atom structure is similar.

Mentions: The all-atom structure of adenylate kinase (4ake) is first surrounded by several layers of water molecules. Subsequently, only water molecules that are within a certain cut-off distance of any protein atom are kept to represent the first layer of ordered water molecules that is captured by SAXS data (Fig. 1a). After testing several cut-off values, we found that a 3.5 Å cut-off produces a P(r) in good agreement with a simulated experimental one obtained from crysol/gnom31 (Fig. 1b).


Normal Mode Flexible Fitting of High-Resolution Structures of Biological Molecules Toward SAXS Data.

Gorba C, Tama F - Bioinform Biol Insights (2010)

Coarse-graining process and scaling for Adenylate Kinase. (a) Adenlynate Kinase surrounded with several layers of water molecules (colored in gray). Only water molecules shown in light blue are considered to estimate the Intensity Scattering profile and consequently derived the P(r). (b) P(r) for the Adenylate Kinase as obtained with eq. 1 or with the program suite Crysol/Gnom. Good agreement between the P(r) is observed. (c) Coarse-graining: adenylate kinase is shown as ribbon, only its Cα atoms are considered (not shown) and from the first shell of water molecules surrounding the protein (transparent gray), only 1/8 of these molecules are kept (light blue). (d) Simulated experimental data using all atom structures: P(r) for the open and close forms of the Adenylate Kinase as derived from the Crysol/Gnom program suite. (e) P(r) for the coarse-grained model of the protein/solvent system as calculated using eq. 1, Pini(r). The target Ptar(r) is prepared by scaling Pexp(r) so that its integral matches the integral of the coarse-grained model Pini(r). Note the good agreement between the scaled P(r) and the P(r) derived from all-atom structure is similar.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2901630&req=5

f1-bbi-2010-043: Coarse-graining process and scaling for Adenylate Kinase. (a) Adenlynate Kinase surrounded with several layers of water molecules (colored in gray). Only water molecules shown in light blue are considered to estimate the Intensity Scattering profile and consequently derived the P(r). (b) P(r) for the Adenylate Kinase as obtained with eq. 1 or with the program suite Crysol/Gnom. Good agreement between the P(r) is observed. (c) Coarse-graining: adenylate kinase is shown as ribbon, only its Cα atoms are considered (not shown) and from the first shell of water molecules surrounding the protein (transparent gray), only 1/8 of these molecules are kept (light blue). (d) Simulated experimental data using all atom structures: P(r) for the open and close forms of the Adenylate Kinase as derived from the Crysol/Gnom program suite. (e) P(r) for the coarse-grained model of the protein/solvent system as calculated using eq. 1, Pini(r). The target Ptar(r) is prepared by scaling Pexp(r) so that its integral matches the integral of the coarse-grained model Pini(r). Note the good agreement between the scaled P(r) and the P(r) derived from all-atom structure is similar.
Mentions: The all-atom structure of adenylate kinase (4ake) is first surrounded by several layers of water molecules. Subsequently, only water molecules that are within a certain cut-off distance of any protein atom are kept to represent the first layer of ordered water molecules that is captured by SAXS data (Fig. 1a). After testing several cut-off values, we found that a 3.5 Å cut-off produces a P(r) in good agreement with a simulated experimental one obtained from crysol/gnom31 (Fig. 1b).

Bottom Line: We present a method to reconstruct a three-dimensional protein structure from an atomic pair distribution function derived from the scattering intensity profile from SAXS data by flexibly fitting known x-ray structures.For computational efficiency, the protein and water molecules included in the protein first hydration shell are coarse-grained.Illustrative results of our flexible fitting studies on simulated SAXS data from five different proteins are presented.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, The University of Arizona, 1041 E. Lowell Street, Tucson, AZ, 85721.

ABSTRACT
We present a method to reconstruct a three-dimensional protein structure from an atomic pair distribution function derived from the scattering intensity profile from SAXS data by flexibly fitting known x-ray structures. This method uses a linear combination of low-frequency normal modes from an elastic network description of the molecule in an iterative manner to deform the structure to conform optimally to the target pair distribution function derived from SAXS data. For computational efficiency, the protein and water molecules included in the protein first hydration shell are coarse-grained. In this paper, we demonstrate the validity of our coarse-graining approach to study SAXS data. Illustrative results of our flexible fitting studies on simulated SAXS data from five different proteins are presented.

No MeSH data available.