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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.


Conformational change of the LAO binding protein obtained from the normal mode flexible fitting. (a) The P(r) of initial (▪), predicted (gray x) and target (black +) structures are shown. The P(r) of the predicted structure is in close agreement with the target PDF and the structures are also very similar. (b) The initial structure of LAO binding protein (pink), the modeled structure predicted from the fitting algorithm (iceblue) and the target structure from which Ptar(r) was created (silver). (c) and (d) represent the placement of the coarse-grained water molecules in the initial and modeled structures. Arrows indicate the major conformational change of the system.
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f3-bbi-2010-043: Conformational change of the LAO binding protein obtained from the normal mode flexible fitting. (a) The P(r) of initial (▪), predicted (gray x) and target (black +) structures are shown. The P(r) of the predicted structure is in close agreement with the target PDF and the structures are also very similar. (b) The initial structure of LAO binding protein (pink), the modeled structure predicted from the fitting algorithm (iceblue) and the target structure from which Ptar(r) was created (silver). (c) and (d) represent the placement of the coarse-grained water molecules in the initial and modeled structures. Arrows indicate the major conformational change of the system.

Mentions: For the LAO binding protein, the RMSD decreases from 4.7 Å to 2 Å for the best fit. Figure 3a shows the P(r) for the initial, target and best predicted structure. Although the difference in P(r) between initial and target is rather small, i.e. information for refinement is limited, the agreement between the target P(r) and the one for the best predicted structure is good. Superposition of the three structures also reveals good agreement between the modeled structure and the target (Fig. 3b). In particular the opening/closing of the two domains is well captured.


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

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

Conformational change of the LAO binding protein obtained from the normal mode flexible fitting. (a) The P(r) of initial (▪), predicted (gray x) and target (black +) structures are shown. The P(r) of the predicted structure is in close agreement with the target PDF and the structures are also very similar. (b) The initial structure of LAO binding protein (pink), the modeled structure predicted from the fitting algorithm (iceblue) and the target structure from which Ptar(r) was created (silver). (c) and (d) represent the placement of the coarse-grained water molecules in the initial and modeled structures. Arrows indicate the major conformational change of the system.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2901630&req=5

f3-bbi-2010-043: Conformational change of the LAO binding protein obtained from the normal mode flexible fitting. (a) The P(r) of initial (▪), predicted (gray x) and target (black +) structures are shown. The P(r) of the predicted structure is in close agreement with the target PDF and the structures are also very similar. (b) The initial structure of LAO binding protein (pink), the modeled structure predicted from the fitting algorithm (iceblue) and the target structure from which Ptar(r) was created (silver). (c) and (d) represent the placement of the coarse-grained water molecules in the initial and modeled structures. Arrows indicate the major conformational change of the system.
Mentions: For the LAO binding protein, the RMSD decreases from 4.7 Å to 2 Å for the best fit. Figure 3a shows the P(r) for the initial, target and best predicted structure. Although the difference in P(r) between initial and target is rather small, i.e. information for refinement is limited, the agreement between the target P(r) and the one for the best predicted structure is good. Superposition of the three structures also reveals good agreement between the modeled structure and the target (Fig. 3b). In particular the opening/closing of the two domains is well captured.

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.