Abstract
Studies of interactions between protein domains and ligands are important in many aspects such as cellular signaling. We present a knowledge-guided approach for docking protein domains and flexible ligands. The approach is applied to the WW domain, a small protein module mediating signaling complexes which have been implicated in diseases such as muscular dystrophy and Liddle’s syndrome. The first stage of the approach employs a substring search for two binding grooves of WW domains and possible binding motifs of peptide ligands based on known features. The second stage aligns the ligand’s peptide backbone to the two binding grooves using a quasi-Newton constrained optimization algorithm. The backbone-aligned ligands produced serve as good starting points to the third stage which uses any flexible docking algorithm to perform the docking. The experimental results demonstrate that the backbone alignment method in the second stage performs better than conventional rigid superposition given two binding constraints. It is also shown that using the backbone-aligned ligands as initial configurations improves the flexible docking in the third stage. The presented approach can also be applied to other protein domains that involve binding of flexible ligand to two or more binding sites.
This research is supported by NUS R-252-000-293-112.
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Keywords
- Root Mean Square Deviation
- Protein Docking
- Flexible Ligand
- Docking Algorithm
- Average Root Mean Square Deviation
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
References
Adzhubei, A.A., Sternberg, M.J.E.: Left-handed polyproline II helices commonly occur in globular proteins. Journal of Molecular Biology 229, 472–493 (1993)
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)
Bork, P., Sudol, M.: The WW domain: a protein module that binds proline-rich or proline-containing ligands (2000)
Case, D.A., Cheatham, T.E., Darden, T., Gohlke, H., Luo, R., Merz Jr., K.M., Onufriev, A., Simmerling, C., Wang, B., Woods, R.J.: The amber biomolecular simulation programs. Journal of Computational Chemistry 26, 1668–1688 (2005)
Chen, R., Li, L., Weng, Z.: ZDOCK: an initial-stage protein-docking algorithm. Proteins 52, 80–87 (2003)
Dominguez, C., Boelens, R., Bonvin, A.M.: HADDOCK: a protein-protein docking approach based on biochemical or biophysical information. Journal of the American Chemical Society 125(7), 1731–1737 (2003)
Fernández-Recio, J., Totrov, M., Abagyan, R.: ICM-DISCO docking by global energy optimization with fully flexible side-chains. Proteins 52, 113–117 (2003)
Gabb, H.A., Jackson, R.M., Sternberg, M.J.E.: Modelling protein docking using shape complementarity, electrostatics, and biochemical information. Journal of Molecular Biology 272, 106–120 (1997)
Gray, J.J., Moughon, S., Wang, C., Schueler-Furman, O., Kuhlman, B., Rohl, C.A., Baker, D.: Protein-protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations. Journal of Molecular Biology 331, 281–299 (2003)
Halperin, I., Ma, B., Wolfson, H., Nussinov, R.: Principles of docking: An overview of search algorithms and a guide to scoring functions. Proteins 47, 409–443 (2002)
Ilsleya, J.L., Sudolb, M., Windera, S.J.: The WW domain: Linking cell signalling to the membrane cytoskeleton. Cellular Signalling 14, 183–189 (2002)
Jackson, R.M., Gabb, H.A., Sternberg, M.J.: Rapid refinement of protein interfaces incorporating solvation: application to the docking problem. Journal of Molecular Biology 276, 265–285 (1998)
Jones, G., Willett, P., Glen, R.C., Leach, A.R., Taylor, R.: Development and validation of a genetic algorithm for flexible docking. Journal of Molecular Biology 267, 727–748 (1997)
Katchalski-Katzir, E., Shariv, I., Eisenstein, M., Friesem, A., Aflalo, C., Vakser, I.: Molecular surface recognition: Determination of geometric fit between protein and their ligands by correlation techniques. Proceedings of the National Academy of Sciences of the United States of America 89, 2195–2199 (1992)
Kato, Y., Nagata, K., Takahashi, M., Lian, L., Herrero, J.J., Sudol, M., Tanokura, M.: Common mechanism of ligand recognition by group II/III WW domains. Journal of Biological Chemistry 279(30), 31833–31841 (2004)
Li, L., Chen, R., Weng, Z.: RDOCK: refinement of rigid-body protein docking predictions. Proteins 53, 693–707 (2003)
Macias, M.J., Wiesner, S., Sudol, M.: Ww and sh3 domains, two different scaffolds to recognize proline-rich ligands. FEBS Letters 53(1), 30–37 (2002)
Makino, S., Kuntz, I.D.: Automated flexible ligand docking method and its application for database search. Journal of Computational Chemistry 18, 1812–1825 (1997)
Mandell, J.G., Roberts, V.A., Pique, M.E., Kotlovyi, V., Mitchell, J.C., Nelson, E., Tsigelny, I., Ten Eyck, L.F.: Protein docking using continuum electrostatics and geometric fit. Protein Engineering 14, 105–113 (2001)
Morris, G.M., Goodsell, D.S., Halliday, R.S., Huey, R., Hart, W.E., Belew, R.K., Olson, A.J.: Automated docking using a lamarckian genetic algorithm and and empirical binding free energy function. Journal of Computational Chemistry 19, 1639–1662 (1998)
Press, W.H., Teukolsky, S.A., Vetterling, W.T., Flannery, B.P.: Numerical Recipes in C++: The Art of Scientific Computing. Cambridge University Press, Cambridge (2002)
Rarey, M., Kramer, B., Lengauer, T., Klebe, G.: A fast flexible docking method using an incremental construction algorithm. Journal of Molecular Biology 261, 470–489 (1996)
Ritchie, D., Kemp, G.: Protein docking using spherical polar Fourier correlations. Proteins 39(2), 178–194 (2000)
Sudol, M.: Structure and function of the WW domain. Progress in Biophysics and Molecular Biology 65(1-2), 113–132 (1996)
Sudol, M.: From src homology domains to other signaling modules: proposal of the ‘protein recognition code’. Oncogene 17, 1469–1474 (1998)
Totrov, M., Abagyan, R.: Flexible protein-ligand docking by global energy optimization in internal coordinates. Proteins 1, 215–220 (1997)
Tovchigrechko, A., Vakser, I.A.: GRAMM-X public web server for protein-protein docking. Nucleic Acids Research 314, W310–W314 (2006)
Vakser, I.A.: Protein docking for low-resolution structures. Protein Engineering 8, 371–377 (1995)
Zarrinpar, A., Bhattacharyya, R.P., Lim, W.A.: The structure and function of proline recognition domains. Science’s STKE 179, re8 (2003)
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Lu, H., Li, H., Banu Bte Sm Rashid, S., Leow, W.K., Liou, YC. (2009). Knowledge-Guided Docking of WW Domain Proteins and Flexible Ligands. In: Kadirkamanathan, V., Sanguinetti, G., Girolami, M., Niranjan, M., Noirel, J. (eds) Pattern Recognition in Bioinformatics. PRIB 2009. Lecture Notes in Computer Science(), vol 5780. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-04031-3_16
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DOI: https://doi.org/10.1007/978-3-642-04031-3_16
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