Skip to main content
Springer Nature Link
Log in

Protein Conformational Flexibility Analysis with Noisy Data

  • Conference paper
Research in Computational Molecular Biology (RECOMB 2007)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 4453))

Abstract

Protein conformational changes play a critical role in biological functions such as ligand-protein and protein-protein interactions. Due to the noise in structural data, determining salient conformational changes reliably and efficiently is a challenging problem. This paper presents an efficient algorithm for analyzing protein conformational changes, using noisy data. It applies a statistical flexibility test to all contiguous fragments of a protein and combines the information from these tests to compute a consensus flexibility measure for each residue of the protein. We tested the algorithm, using data from the Protein Data Bank and the Macromolecular Movements Database. The results show that our algorithm can reliably detect different types of salient conformational changes, including well-known examples such as hinge well as the flap motion of HIV-1 proteaseThe software implementing software implementing our algorithm is available at http://motion.comp.nus.edu.sg/projects/proflexana/proflexana.html .

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  1. Anderson, B.F., Baker, H.M., Norris, G.E., Rumball, S.V., Baker, E.N.: Apolactoferrin structure demonstrates ligand-induced conformational change in transferrins. Nature 344, 784–787 (1990)

    Article  Google Scholar 

  2. Chew, L.P., Huttenlocher, D., Kedem, K., Kleinberg, J.: Fast detection of common geometric substructure in proteins. In: Proc. ACM Int. Conf. on Computational Biology (RECOMB), pp. 104–113. ACM Press, New York (1999)

    Google Scholar 

  3. Echols, N., Milburn, D., Gerstein, M.: MolMovDB: Analysis and Visualization of Conformational Change and Structural Flexibility. Nucleic Acids Res. 31(1), 478–482 (2003), http://molmovdb.mbb.yale.edu/molmovdb/

    Article  Google Scholar 

  4. Gerstein, M., Altman, R.B.: Average core structures and variability measures for protein families: Application to the immunoglobins. J. Mol. Biol. 251, 161–175 (1995)

    Article  Google Scholar 

  5. Gerstein, M., Anderson, B.F., Norris, G.E., Baker, E.N., Lesk, A.M., Chothia, C.: Domain Closure in Lactoferrin. J. Mol. Biol. 234, 357–372 (1993)

    Article  Google Scholar 

  6. Gerstein, M., Chothia, C.: Analysis of protein loop closure: Two types of hinges produce one motion in lactate dehydrogenase. J. Mol. Biol. 220(1), 133–149 (1991)

    Article  Google Scholar 

  7. Gerstein, M., Jansen, R., Johnson, T., Tsai, J., Krebs, W.: Motions in a Database Framework: from Structure to Sequence. In: Thorpe, M.F., Duxbury, P.M. (eds.) Rigidity Theory and Applications, pp. 401–442. Kluwer Academic Publishers, Dordrecht (1999)

    Google Scholar 

  8. Hopper, P., Harrison, S.C., Sauer, R.T.: Structure of tomato bushy stunt virus. V. Coat protein sequence determinations and its structural implications. J. Mol. Biol. 177(4), 701–713 (1984)

    Article  Google Scholar 

  9. Horn, B.K.P.: Closed-form solution of absolute orientation using unit quaternions. Journal of the Optical Society A 4(4), 629–642 (1987)

    Article  MathSciNet  Google Scholar 

  10. Huang, E.S., Rock, E.P., Subbiah, S.: Automatic and accurate method for analysis of proteins that undergo hinge-mediated domain and loop movements. Curr. Biol. 3(11), 740–748 (1993)

    Article  Google Scholar 

  11. Jacobs, D.J., Rader, A.J., Kuhn, L.A., Thorpe, M.F.: Protein Flexibility Predications Using Graph Theory. Proteins: Structure, Function, and Genetics 44(2), 150–165 (2001)

    Article  Google Scholar 

  12. Joseph, D., Petsko, G.A., Karplus, M.: Anatomy of a Conformational Change: Hinged ”Lid” Motion of the Triose Phosphate Isomerase Loop. Science 249, 1425–1428 (1990)

    Article  Google Scholar 

  13. Korn, A.P., Rose, D.R.: Torsion angle differences as a means of pinpointing local polypeptide chain trajectory changes for identical proteins in different conformational states. Protein Engineering 7, 961–967 (1994)

    Article  Google Scholar 

  14. Krebs, W.G., Alexandrov, V., Wilson, C.A., Echols, N., Yu, H., Gerstein, M.: Normal mode analysis of macromolecular motions in a database framework: Developing mode concentration as a useful classifying statistic. Proteins: Structure, Function, and Genetics 48(4), 682–695 (2002)

    Article  Google Scholar 

  15. Lesk, A.M.: Protein Architecture: A Practical Approach. Oxford University Press, Oxford (1991)

    Google Scholar 

  16. Levine, M., Stuart, D., Williams, J.: A method for systematic comparison of the three-dimensional structures of proteins and some results. Acta Crystallography A40, 600–610 (1984)

    Google Scholar 

  17. Nigham, A., Hsu, D.: Protein conformational flexibility analysis with noisy data. Technical Report TRD1/07, National University of Singapore, School of Computing (Jan. 2007)

    Google Scholar 

  18. Nishikawa, A., Ooi, T., Isogai, Y., Saito, N.: Tertiary structure of proteins. J Phys. Soc. Jpn. 32, 1333–1337 (1972)

    Google Scholar 

  19. Perryman, A.L., Lin, J., McCammon, A.: HIV-1 protease molecular dynamics of a wild-type and of the V82F/I84V mutant: Possible contributions to drug resistance and a potential new target site for drugs. Protein Science 13, 1108–1123 (2004)

    Article  Google Scholar 

  20. Shatsky, M., Wolfson, H.J., Nussinov, R.: Flexible protein alignment and hinge detection. Proteins: Structure, Function and Genetics 48, 242–256 (2002)

    Article  Google Scholar 

  21. Shibuya, T.: Geometric Suffix Tree: A New Index Structure for Protein 3-D Structures. In: Lewenstein, M., Valiente, G. (eds.) CPM 2006. LNCS, vol. 4009, pp. 84–93. Springer, Heidelberg (2006)

    Chapter  Google Scholar 

  22. Subbiah, S.: Protein Motions. Chapman & Hall, Boca Raton (1996)

    Google Scholar 

  23. Teodoro, M., Phillips Jr., G.N., Kavraki, L.E.: A Dimensionality Reduction Approach to Modeling Protein Flexibility. In: Proc. ACM Int. Conf. on Computational Biology (RECOMB), pp. 299–308. ACM Press, New York (2002)

    Chapter  Google Scholar 

  24. Thompson, T.B., Thomas, M.G., Escalante-Semerena, J.C., Rayment, I.: Three-dimensional structure of adenosylcobinamide kinase/adenosylcobinamide phosphate guanylyltransferase from Salmonella typhimurium determined to 2.3 A resolution. Biochemistry 37(21), 7686–7695 (1998)

    Article  Google Scholar 

  25. Vihinen, M., Torkkila, E., Riikonen, P.: Accuracy of protein flexibility predictions. Proteins 19(2), 141–149 (1994)

    Article  Google Scholar 

  26. Wriggers, W., Schulten, K.: Protein domain movements: Detection of rigid domains and visualization of hinges in comparisons of atomic coordinates. Proteins: Structure, Function, and Genetics 29, 1–14 (1997)

    Article  Google Scholar 

  27. Ye, Y., Godzik, A.: Flexible structure alignment by chaining aligned fragment pairs allowing twists. Bioinformatics 19(Suppl. 2), ii246–ii255 (2003)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Singapore–MIT Alliance, Singapore 117576, Singapore

    Anshul Nigham

  2. National University of Singapore, Singapore 117543, Singapore

    David Hsu

Authors
  1. Anshul Nigham
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Hsu
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Terry Speed Haiyan Huang

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer Berlin Heidelberg

About this paper

Cite this paper

Nigham, A., Hsu, D. (2007). Protein Conformational Flexibility Analysis with Noisy Data. In: Speed, T., Huang, H. (eds) Research in Computational Molecular Biology. RECOMB 2007. Lecture Notes in Computer Science(), vol 4453. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-71681-5_28

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-71681-5_28

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-71680-8

  • Online ISBN: 978-3-540-71681-5

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics