Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Dec 7;101(11):2770-81.
doi: 10.1016/j.bpj.2011.10.046.

Improving protein template recognition by using small-angle x-ray scattering profiles

Marcelo Augusto dos Reis  1 , Ricardo Aparicio, Yang Zhang
Affiliations

Improving protein template recognition by using small-angle x-ray scattering profiles

Marcelo Augusto dos Reis et al. Biophys J. .

Abstract

Small-angle x-ray scattering (SAXS) is able to extract low-resolution protein shape information without requiring a specific crystal formation. However, it has found little use in atomic-level protein structure determination due to the uncertainty of residue-level structural assignment. We developed a new algorithm, SAXSTER, to couple the raw SAXS data with protein-fold-recognition algorithms and thus improve template-based protein-structure predictions. We designed nine different matching scoring functions of template and experimental SAXS profiles. The logarithm of the integrated correlation score showed the best template recognition ability and had the highest correlation with the true template modeling (TM)-score of the target structures. We tested the method in large-scale protein-fold-recognition experiments and achieved significant improvements in prioritizing the best template structures. When SAXSTER was applied to the proteins of asymmetric SAXS profile distributions, the average TM-score of the top-ranking templates increased by 18% after homologous templates were excluded, which corresponds to a p-value < 10(-9) in Student's t-test. These data demonstrate a promising use of SAXS data to facilitate computational protein structure modeling, which is expected to work most efficiently for proteins of irregular global shape and/or multiple-domain protein complexes.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Flow chart of SAXSTER, combining SAXS data and MUSTER for protein structure prediction.
Figure 2
Figure 2
Comparison of the experimental SAXS profiles with those obtained by the CG model in both reciprocal (left) and real (right) spaces. (A and A′) PF1282 P. furiosus, with SAXS data and structural model taken from the BIOISIS databank (BIOISIS ID: 1RBDGP). (B and B′) Lysozyme, with SAXS data from CRYSOL and structure model from the PDB (PDB ID: 6LYZ). (C and C′) PF1528 P. furiosus, with SAXS data and structural model from BIOISIS (BIOISIS ID: 1AMIGP). (D and D′) U2AF65 Splicing factor, with SAXS data and structural model from BIOISIS (BIOISIS ID: 1U2FKP). (E and E′) HSA, with SAXS data from our unpublished data and structure from a homologous protein in the PDB (PDB ID: 1AO6A).
Figure 3
Figure 3
TM-score of the first templates selected by SAXSTER versus that obtained by MUSTER. SAXS scoring functions for SAXSTER are in reciprocal space (left column) and real space (right column), respectively. Full-length models were built from a threading alignment by random walk (A and B), MODELLER (C and D), and I-TASSER (E and F).
Figure 4
Figure 4
Representative examples of the protein templates selected by MUSTER and SAXSTER. Blue, red, and green cartoons represent the target structure, model from MUSTER ranking, and model from SAXSTER ranking, respectively. SAXS profiles in reciprocal and real spaces are shown for each case following the same color codes. The targets are from PDB entries (A) 2FKCA, (B) 2PJPA, (C) 2W4YA, (D) 2RKLA, and (E) 3KLRA. The black main chain in E is a SAXSTER model with loops generated by I-TASSER; all other models have loops generated by MODELLER.
Figure 5
Figure 5
TM-score of the first templates obtained by SAXSTER versus those obtained by MUSTER for 141 hard proteins with asymmetric SAXS profile distributions. The full-length models were constructed by random walk with the SAXS profile calculated in real space.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kopp J., Bordoli L., Schwede T. Assessment of CASP7 predictions for template-based modeling targets. Proteins. 2007;69(Suppl 8):38–56. - PubMed
    1. Cozzetto D., Kryshtafovych A., Tramontano A. Evaluation of template-based models in CASP8 with standard measures. Proteins. 2009;77(Suppl 9):18–28. - PMC - PubMed
    1. Berman H.M., Westbrook J., Bourne P.E. The Protein Data Bank. Nucleic Acids Res. 2000;28:235–242. - PMC - PubMed
    1. Bowie J.U., Lüthy R., Eisenberg D. A method to identify protein sequences that fold into a known three-dimensional structure. Science. 1991;253:164–170. - PubMed
    1. Jones D.T., Taylor W.R., Thornton J.M. A new approach to protein fold recognition. Nature. 1992;358:86–89. - PubMed

Publication types

LinkOut - more resources