Abstract
We introduce two GALAXY web servers called GalaxySite and GalaxyPepDock that predict protein complex structures with small organic compounds and peptides, respectively. GalaxySite predicts ligands that may bind the input protein and generates complex structures of the protein with the predicted ligands from the protein structure given as input or predicted from the input sequence. GalaxyPepDock takes a protein structure and a peptide sequence as input and predicts structures for the protein–peptide complex. Both GalaxySite and GalaxyPepDock rely on available experimentally resolved structures of protein–ligand complexes evolutionarily related to the target. With the continuously increasing size of the protein structure database, the probability of finding related proteins in the database is increasing. The servers further relax the complex structures to refine the structural aspects that are missing in the available structures or that are not compatible with the given protein by optimizing physicochemical interactions. GalaxyPepDock allows conformational change of the protein receptor induced by peptide binding. The atomistic interactions with ligands predicted by the GALAXY servers may offer important clues for designing new molecules or proteins with desired binding properties.
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References
Kristiansen K (2004) Molecular mechanisms of ligand binding, signaling, and regulation within the superfamily of G-protein-coupled receptors: molecular modeling and mutagenesis approaches to receptor structure and function. Pharmacol Ther 103(1):21–80. doi:10.1016/j.pharmthera.2004.05.002
Negri A, Rodriguez-Larrea D, Marco E, Jimenez-Ruiz A, Sanchez-Ruiz JM, Gago F (2010) Protein-protein interactions at an enzyme-substrate interface: characterization of transient reaction intermediates throughout a full catalytic cycle of Escherichia coli thioredoxin reductase. Proteins 78(1):36–51. doi:10.1002/prot.22490
Pawson T, Nash P (2000) Protein-protein interactions define specificity in signal transduction. Genes Dev 14(9):1027–1047
Campbell SJ, Gold ND, Jackson RM, Westhead DR (2003) Ligand binding: functional site location, similarity and docking. Curr Opin Struct Biol 13(3):389–395
Kinoshita K, Nakamura H (2003) Protein informatics towards function identification. Curr Opin Struct Biol 13(3):396–400
Laurie AT, Jackson RM (2006) Methods for the prediction of protein-ligand binding sites for structure-based drug design and virtual ligand screening. Curr Protein Pept Sci 7(5):395–406
Sotriffer C, Klebe G (2002) Identification and mapping of small-molecule binding sites in proteins: computational tools for structure-based drug design. Farmaco 57(3):243–251
Damborsky J, Brezovsky J (2014) Computational tools for designing and engineering enzymes. Curr Opin Chem Biol 19:8–16. doi:10.1016/j.cbpa.2013.12.003
Feldmeier K, Hocker B (2013) Computational protein design of ligand binding and catalysis. Curr Opin Chem Biol 17(6):929–933
Tripathi A, Kellogg GE (2010) A novel and efficient tool for locating and characterizing protein cavities and binding sites. Proteins 78(4):825–842. doi:10.1002/prot.22608
Lopez G, Ezkurdia I, Tress ML (2009) Assessment of ligand binding residue predictions in CASP8. Proteins 77(Suppl 9):138–146. doi:10.1002/prot.22557
Lopez G, Rojas A, Tress M, Valencia A (2007) Assessment of predictions submitted for the CASP7 function prediction category. Proteins 69(Suppl 8):165–174. doi:10.1002/prot.21651
Oh M, Joo K, Lee J (2009) Protein-binding site prediction based on three-dimensional protein modeling. Proteins 77(Suppl 9):152–156. doi:10.1002/prot.22572
Ko J, Park H, Heo L, Seok C (2012) GalaxyWEB server for protein structure prediction and refinement. Nucleic Acids Res 40(Web Server Issue):W294–W297. doi:10.1093/nar/gks493
Heo L, Shin WH, Lee MS, Seok C (2014) GalaxySite: ligand-binding-site prediction by using molecular docking. Nucleic Acids Res 42(Web Server Issue):W210–W214. doi:10.1093/nar/gku321
Gallo Cassarino T, Bordoli L, Schwede T (2014) Assessment of ligand binding site predictions in CASP10. Proteins 82(Suppl 2):154–163. doi:10.1002/prot.24495
Schmidt T, Haas J, Gallo Cassarino T, Schwede T (2011) Assessment of ligand-binding residue predictions in CASP9. Proteins 79(Suppl 10):126–136. doi:10.1002/prot.23174
Lee H, Heo L, Lee MS, Seok C (2015) GalaxyPepDock: a protein-peptide docking tool based on interaction similarity and energy optimization. Nucleic Acids Res. doi:10.1093/nar/gkv495
Lensink MF, Wodak SJ (2013) Docking, scoring, and affinity prediction in CAPRI. Proteins 81(12):2082–2095. doi:10.1002/prot.24428
Ko J, Park H, Seok C (2012) GalaxyTBM: template-based modeling by building a reliable core and refining unreliable local regions. BMC Bioinformatics 13:198. doi:10.1186/1471-2105-13-198
Bernstein FC, Koetzle TF, Williams GJ, Meyer EF Jr, Brice MD, Rodgers JR, Kennard O, Shimanouchi T, Tasumi M (1977) The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol 112(3):535–542
Wallace AC, Laskowski RA, Thornton JM (1995) LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng 8(2):127–134
Zhang Y, Skolnick J (2005) TM-align: a protein structure alignment algorithm based on the TM-score. Nucleic Acids Res 33(7):2302–2309. doi:10.1093/nar/gki524
London N, Movshovitz-Attias D, Schueler-Furman O (2010) The structural basis of peptide-protein binding strategies. Structure 18(2):188–199. doi:10.1016/j.str.2009.11.012
Saladin A, Rey J, Thevenet P, Zacharias M, Moroy G, Tuffery P (2014) PEP-SiteFinder: a tool for the blind identification of peptide binding sites on protein surfaces. Nucleic Acids Res 42(Web Server issue):W221–226. doi:10.1093/nar/gku404
Acknowledgement
This work was supported by the National Research Foundation of Korea grants funded by the Ministry of Science, ICT & Future Planning (No. 2013R1A2A1A09012229).
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Heo, L., Lee, H., Baek, M., Seok, C. (2016). Binding Site Prediction of Proteins with Organic Compounds or Peptides Using GALAXY Web Servers. In: Stoddard, B. (eds) Computational Design of Ligand Binding Proteins. Methods in Molecular Biology, vol 1414. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3569-7_3
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DOI: https://doi.org/10.1007/978-1-4939-3569-7_3
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