Abstract
The need to determine phases is a major bottleneck in a fully automated X-ray crystallography pipeline. The problem commonly called phasing can be solved by a computational method called molecular replacement (MR). With the deposition of more and more proteins into the Protein Data Bank (PDB), it has been shown that the MR yields better initial models. In this paper, ab initio first model generation is addressed. A novel scheme using PHASER is proposed which does not require any a priori information about the structure. The input to the system is the target structure factors and the sequence. We created a unique set of supersecondary structure (fragment) dataset and used them in creation of the first model. The method was evaluated with log-likelihood gain (LLG) and translational Z-score (TFZ) as defined by PHASER. The results obtained are highly encouraging with translation Z-scores of 7 and above for the first model. The proposed scheme is tested on six proteins, two each from α, β and α + β classes with very good results.
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
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, 235–242 (2000)
Abola, E., Kuhn, P., Earnest, T., Stevens, R.C.: Automation of x-ray crystallography. Nature structural biology, Structural Genomic Supplement 973–977 (2000)
Lamzin, V.S., Perrakis, A.: Current state of automated crystallographic data analysis. Nature structural biology, Structural Genomic Supplement 978–981 (2000)
Drenth, J.: Principles of Protein X-Ray Crystallography, 2nd edn. Springer, New York (1999)
Rhodes, G.: Crystallography Made Crystal Clear, 2nd edn. Academic Press, San Diego (2000)
Rossmann, M.G., Blow, D.M.: The detection of sub-units within the crystallographic asymmetric unit. Acta Crystallographica 15, 24–31 (1962)
Jones, D.T.: Evaluating the potential of using fold-recognition models for molecular replacement. Acta Crystallographica D57, 1428–1434 (2001)
Rost, B.: Twilight zone of protein sequence alignments. Protein Engineering 12(2), 85–94 (1999)
Schwarzenbacher, R., Godzik, A., Grzenchnik, S.K., Jaroszewski, L.: The importance of alignment accuracy for molecular replacement. Acta Crystallographica D60, 1229–1236 (2004)
Collaborative Computational Project Number 4. The CCP4 suite: programs for protein crystallography. Acta Crystallographica Section D, 50(5), pp.760–763 (1994)
McCoy, A.J.: Solving structures of protein complexes by mlecular replacement with Phaser. Acta Crystallographica D63, 32–41 (2007)
Read, R.J.: Pushing the boundaries of molecular replacement with maximum likelihood. Acta Crystallographica D57, 1373–1382 (2001)
Navaza, G.: AMORE: an automated package for molecular replacement. Acta Crystallographica A50, 157–163 (1994)
Vagin, A., Teplyakov, A.: MOLREP: an automated program for molecular replacement. Journal of Applied Crystallography 30, 1022–1025 (1997)
Claude, J.-B., Suhre, K., Notredame, C., Claverie, C., Abergel, J.M.: CaspR: a web-server for automated molecular replacement using homology modelling. Nucleic Acids Research 32, W606–W609 (2004)
Bahar, M., et al.: Others. SPINE workshop on automated X-ray analysis: a progress report. Acta Crystallographica D62, 1170–1183 (2006)
Long, F., Vagin, A.A., Murshudov, G.N.: Complete automation of molecular replacement in BALBES. CCP4 Study Weekend (abstract, 2007)
Strop, P., Brzustowicz, M.R., Brunger, A.T.: Ab initio molecular replacement phasing for symmetric helical membrane proteins. Acta Crystallographica D63, 188–196 (2007)
Webster, G., Hilgenfeld, R.: An evolutionary computational approach to the phase problem in macromolecular X-ray crystallography. Acta Crystallographica A57, 351–358 (2001)
Cowtan, K.: Modified Phased Translation Functions and their application to Molecular-Fragment location. Acta Crystallographica D54, 750–756 (1998)
Terwilliger, T.C.: Automated main-chain model building by template matching and iterative fragment extension. Acta Crystallographica D59, 38–44 (2003)
Orengo, C.A., Michie, A.D., Jones, S., Jones, D.T., Swindells, M.B., Thornton, J.M.: Cath- a hierarchic classification of protein domain structures. Structure 5(8), 1093–1108 (1997)
Gubbi, J., Shilton, A., Parker, M., Palaniswami, M.: Protein topology classification using two-stage support vector machines. Genome Informatics 17(2), 259–269 (2006)
Guex, N., Peitsch, M.C.: SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling. Electrophoresis 18, 2714–2723 (1997)
Author information
Authors and Affiliations
Editor information
Rights and permissions
Copyright information
© 2007 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Gubbi, J., Parker, M., Palaniswami, M. (2007). Solving Protein Structures Using Molecular Replacement Via Protein Fragments. In: Masulli, F., Mitra, S., Pasi, G. (eds) Applications of Fuzzy Sets Theory. WILF 2007. Lecture Notes in Computer Science(), vol 4578. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-73400-0_80
Download citation
DOI: https://doi.org/10.1007/978-3-540-73400-0_80
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-73399-7
Online ISBN: 978-3-540-73400-0
eBook Packages: Computer ScienceComputer Science (R0)