Abstract
This article provides the initial results of our effort to develop a hybrid prediction method, combining the principles of de novo and homology modeling, to help solve the protein three-dimensional (3-D) structure prediction problem. A target protein amino acid sequence is fragmented into many short contiguous fragments. Clustered short templates fragments, obtained from experimental protein structures in the Protein Data Bank (PDB), using the NCBI BLASTp program, were used for building an initial conformation, which was further refined by molecular dynamics simulations. We tested our method with the artificially designed alpha helical hairpin (PDB ID: 1ZDD) starting with its amino acids sequence only. The structure obtained with the proposed method is topologically a helical hairpin, with a C( RMSD of ~ 5.0 Å with respect to the experimental PDB structure for all 34 amino acids residues, and only ~ 2.0 Å when considering amino acids 1 to 22. We discuss further improvements to the method.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Baxevanis, A.D., Ouellette, B.F.F.: Bioinformatics: A Practical Guide to the Analysis of Genes and Proteins, 560 p. Wiley and Sons, Hoboken (2005)
Branden, C., Tooze, J.: Introduction to Protein Structure, 410 p. Garlang Publishing Inc., New York (1998)
Anfinsen, C.B., Haber, E., Sela, M., White Jr., F.H.: Proceedings of the National Academy of Sciences USA. 47, 1309–1314 (1961)
Creighton, T.E.: Protein Folding. Biochemical Journal 270, 1–16 (1990)
Bujnicki, J.M.: Protein Structure Prediction by Recombination of Fragments. Chembiochem. 7(1), 19–27 (2006)
Tramontano, A.: Protein Structure Prediction, 228 p. John Wiley and Sons, Weinheim (2006)
Osguthorpe, D.J.: Ab initio Protein Folding. Current Opinion in Structural Biology 10, 146–152 (2000)
Moult, J.: A Decade of CASP: Progress, Bottlenecks and Prognosis in Protein Structure Prediction. Current Opinion in Structural Biology 15, 285–289 (2005)
Tramontano, A., Morea, V.: Assessment of homology based predictions in CASP5. Proteins: Structure, Function, and Bioinformatics 53, 352–368 (2003)
Kolinski, A.: Protein Modeling and Structure Prediction with a Reduced Representation. Acta Biochimica Polonica 51, 349–371 (2004)
Jones, D.T., Taylort, W.R., Thornton, J.M.: A New Approach to Protein Fold. Nature 358, 86–89 (1992)
Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., Bourne, P.E.: The Protein Data Bank. Nucleic Acids Research 28(1), 235–242 (2000)
Marti-Renom, M.A., Stuart, A., Fiser, A., Sánchez, R., Melo, F., Sali, A.: Comparative Protein Structure Modeling of genes and genomes. Annual Review of Biophysics and Biomolecular Structure 29, 291–325 (2000)
Ngo, J.T., Marks, J., Karplus, M.: Computational Complexity, protein structure prediction and the Levinthal Paradox. In: Merz Jr., K., Grand, S.L. (eds.) The Protein Folding Problem and Tertiary Structure Prediction, ch. 14, pp. 435–508. Birkhäuser, Boston (1997)
Levinthal, C.: Are there pathways for protein folding? Journal de Chimie Physique et de Physico-Chimie Biologique 65, 44–45 (1968)
Altschul, S.F., Madden, T.L., Schäffer, A.A., Zhang, J., Zhang, Z., Miller, W., Lipman, D.J.: Gapped BLAST and PSI-BLAST: a New Generation of Protein Database Search Programs. Nucleic Acids Research 25, 3389–3402 (1997)
Chapman, B., Chang, J.: Biopython: Python Tools for Computational Biology. ACM SIGBIO Newsletter 20(2), 15–19 (2002)
Ramachandran, G.N., Sasisekharan, V.: Advances in Protein Chemistry 23, 238–437 (1968)
Hovmöller, T.Z., Ohlson, T.: Conformation of Amino Acids in Proteins. Acta Crystallographica D58, 768–776 (2002)
Witten, I.H., Frank, E.: Data Mining: Practical Machine Learning Tools and Techniques, 2nd edn., 525 p. Elsevier, San Francisco (2005)
Case, D.A., Cheatham, T.E., Darden, T., Gohlke, H., Luo, R., Merz, K.M., Onufriev, A., Simmerling, C., Wang, B., Woods, R.J.: The AMBER Biomolecular Simulation Programs. Journal of Computational Chemistry 26(16), 1668–1688 (2005)
Cornell, W.D., Cieplak, P., Bayly, C.I., Gould, I.R., Merz Jr., K.M., Ferguson, D.M., Spellmeyer, D.C., Fox, T., Caldwell, J.W., Kollman, P.A.: A Second Generation Force Field for the Simulation of Proteins. Journal of the American Chemical Society 117, 5179–5197 (1995)
Starovasnik, M.A., Braisted, A.C., Wells, J.A.: Structural Mimicry of a Native Protein by a Minimized Binding Domain. Proceedings of the National Academy of Sciences USA 94, 10080–10085 (1997)
Murzin, A.G., Brenner, S.E., Hubbard, T., Chothia, C.: SCOP: a Structural Classification of Proteins Database for the Investigation of Sequences and Structures. Journal of Molecular Biology 247, 536–540 (1995)
Bashford, D., Case, D.A.: Generalized Born Models of Macromolecular Solvation Effects. Annual Review Physical Chemistry 51, 129–152 (2000)
Ryckaert, J.P., Ciccotti, G., Berendsen, H.J.C.: Numerical Integration of the Cartesian Equation of Motion of a System with Constraints: Molecular Dynamics of N-alkanes. Journal of Computational Physics 23, 327–341 (1977)
Guex, N., Peitsch, M.C.: SWISS-MODEL and The Swiss-PdbViewer: An Environment for Comparative Protein Modeling. Electrophoresis 18, 2714–2723 (1997)
DeLano, W.L.: The PyMOL Molecular Graphics System. DeLano Scientific, San Carlos (2002)
Laskowski, R.A., MacArthur, M.W., Moss, D.S., Thornton, J.M.: PROCHECK: A Program to Check the Stereochemical Quality of Protein Structures. Journal of Applied Crystallography 26, 283–291 (1993)
Kabsch, W., Sander, C.: Dictionary of Protein Secondary Structure: Pattern Recognition of Hydrogen-Bonded and Geometrical Features. Biopolymers 22, 2577–2637 (1983)
Clarke, D.T., Doig, A.J., Stapley, B.J., Jones, G.R.: The alpha-helix Folds on the Millisecond Time Scale. Proceedings of the National Academy of Sciences USA 96, 7232–7237 (1999)
Author information
Authors and Affiliations
Editor information
Rights and permissions
Copyright information
© 2008 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Dorn, M., Breda, A., Norberto de Souza, O. (2008). A Hybrid Method for the Protein Structure Prediction Problem. In: Bazzan, A.L.C., Craven, M., Martins, N.F. (eds) Advances in Bioinformatics and Computational Biology. BSB 2008. Lecture Notes in Computer Science(), vol 5167. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-85557-6_5
Download citation
DOI: https://doi.org/10.1007/978-3-540-85557-6_5
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-85556-9
Online ISBN: 978-3-540-85557-6
eBook Packages: Computer ScienceComputer Science (R0)