From protein-protein interactions to rational drug design: Are computational methods up to the challenge?

Current Topics in Medicinal Chemistry

Volumn 13, Issue 5, 2013, Pages 602-618

  Coelho, Edgar D ^a   Arrais, Joel P ^b   Oliveira, José Luís ^a  

^a UNIVERSITY OF AVEIRO   (Portugal)

^b UNIVERSITY OF COIMBRA   (Portugal)

Author keywords

Disease networks; Drug design; Drug targets; Protein protein interaction

Indexed keywords

AMINO ACID SEQUENCE; AUTOIMMUNE DISEASE; CODON USAGE; DRUG DESIGN; DRUG TARGETING; GENE EXPRESSION; GENE FUSION; HELICOBACTER PYLORI; HUMAN; HUNTINGTON CHOREA; MACHINE LEARNING; MICROARRAY ANALYSIS; NEUROLOGIC DISEASE; NONHUMAN; PATHOGENESIS; PHYLOGENY; PLASMODIUM; PREDICTION; PROTEIN DOMAIN; PROTEIN PROTEIN INTERACTION; REVIEW; SACCHAROMYCES CEREVISIAE; SEQUENCE HOMOLOGY; TRYPANOSOMIASIS; TUMOR GENE;

COMPUTATIONAL BIOLOGY; DRUG DESIGN; HUMANS; PROTEIN BINDING; PROTEIN INTERACTION MAPPING; PROTEINS;

EID: 84878589163     PISSN: 15680266     EISSN: 18734294     Source Type: Journal    
DOI: 10.2174/1568026611313050005     Document Type: Review

References (160)

1. Shoemaker, B. A.; Panchenko, A. R., Deciphering protein-protein interactions. Part I. Experimental techniques and databases. PLoS Comput Biol 2007, 3 (3), e42.
2. Ofran, Y.; Rost, B., Analysing six types of protein-protein interfaces. J Mol Biol 2003, 325 (2), 377-87.
3. Valdar, W. S.; Thornton, J. M., Protein-protein interfaces: analysis of amino acid conservation in homodimers. Proteins 2001, 42 (1), 108-24.
4. Teichmann, S. A., The constraints protein-protein interactions place on sequence divergence. J Mol Biol 2002, 324 (3), 399-407.
5. Nooren, I. M.; Thornton, J. M., Structural characterisation and functional significance of transient protein-protein interactions. J Mol Biol 2003, 325 (5), 991-1018.
6. Aloy, P.; Ceulemans, H.; Stark, A.; Russell, R. B., The relationship between sequence and interaction divergence in proteins. J Mol Biol 2003, 332 (5), 989-98.
7. Littler, S. J.; Hubbard, S. J., Conservation of orientation and sequence in protein domain--domain interactions. J Mol Biol 2005, 345 (5), 1265-79.
8. Panchenko, A. R.; Wolf, Y. I.; Panchenko, L. A.; Madej, T., Evolutionary plasticity of protein families: coupling between sequence and structure variation. Proteins 2005, 61 (3), 535-44.
9. Ito, T.; Chiba, T.; Ozawa, R.; Yoshida, M.; Hattori, M.; Sakaki, Y., A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proceedings of the National Academy of Sciences 2001, 98 (8), 4569-4574.
10. Ho, Y.; Gruhler, A.; Heilbut, A.; Bader, G. D.; Moore, L.; Adams, S. L.; Millar, A.; Taylor, P.; Bennett, K.; Boutilier, K.; Yang, L.; Wolting, C.; Donaldson, I.; Schandorff, S.; Shewnarane, J.; Vo, M.; Taggart, J.; Goudreault, M.; Muskat, B.; Alfarano, C.; Dewar, D.; Lin, Z.; Michalickova, K.; Willems, A. R.; Sassi, H.; Nielsen, P. A.; Rasmussen, K. J.; Andersen, J. R.; Johansen, L. E.; Hansen, L. H.; Jespersen, H.; Podtelejnikov, A.; Nielsen, E.; Crawford, J.; Poulsen, V.; Sorensen, B. D.; Matthiesen, J.; Hendrickson, R. C.; Gleeson, F.; Pawson, T.; Moran, M. F.; Durocher, D.; Mann, M.; Hogue, C. W.; Figeys, D.; Tyers, M., Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spec-trometry. Nature 2002, 415 (6868), 180-3.
11. Zhu, H.; Bilgin, M.; Bangham, R.; Hall, D.; Casamayor, A.; Bertone, P.; Lan, N.; Jansen, R.; Bidlingmaier, S.; Houfek, T.; Mitchell, T.; Miller, P.; Dean, R. A.; Gerstein, M.; Snyder, M., Global Analysis of Protein Activities Using Proteome Chips. Sci ence 2001, 293 (5537), 2101-2105.
12. Sidhu, S. S.; Fairbrother, W. J.; Deshayes, K., Exploring protein-protein interactions with phage display. Chembiochem: a European journal of chemical biology 2003, 4 (1), 14-25.
13. Tong, A. H.; Evangelista, M.; Parsons, A. B.; Xu, H.; Bader, G. D.; Page, N.; Robinson, M.; Raghibizadeh, S.; Hogue, C. W.; Bussey, H.; Andrews, B.; Tyers, M.; Boone, C, Systematic genetic analysis with ordered arrays of yeast deletion mutants. Science 2001, 294 (5550), 2364-8.
14. Ge, H.; Liu, Z.; Church, G. M.; Vidal, M., Correlation between transcriptome and interactome mapping data from Saccharomyces cerevisiae. Nature genetics 2001, 29 (4), 482-6.
15. Kukar, T.; Eckenrode, S.; Gu, Y.; Lian, W.; Megginson, M.; She, J.-X.; Wu, D., Protein Microarrays to Detect Protein-Protein Interactions Using Red and Green Fluorescent Proteins. Analytical Biochemistry 2002, 306 (1), 50-54.
16. Xia, J. F.; Wang, S. L.; Lei, Y. K., Computational methods for the prediction of protein-protein interactions. Protein Pept Lett 2010, 17 (9), 1069-78.
17. Valencia, A.; Pazos, F., Computational methods for the prediction of protein interactions. Curr Opin Struct Biol 2002, 12 (3), 368-73.
18. Gomez, S. M., Prediction of protein-protein interaction networks. Curr Protoc Bioinformatics 2003, Chapter 8, Unit8 2.
19. Szilagyi, A.; Grimm, V.; Arakaki, A. K.; Skolnick, J., Prediction of physical protein-protein interactions. Phys Biol 2005, 2 (2), S1-16.
20. Pitre, S.; Alamgir, M.; Green, J. R; Dumontier, M.; Dehne, F.; Golshani, A., Computational methods for predicting protein-protein interactions. Adv Biochem Eng Biotechnol 2008, 110, 247-67.
21. Skrabanek, L.; Saini, H. K.; Bader, G. D.; Enright, A. J., Computational prediction of protein-protein interactions. Mol Biotechnol 2008, 38 (1), 1-17.
22. Liu, Y.; Kim, I.; Zhao, H., Protein interaction predictions from diverse sources. Drug Discov Today 2008, 13 (9-10), 409-16.
23. Tamames, J.; Casari, G.; Ouzounis, C; Valencia, A., Conserved clusters of functionally related genes in two bacterial genomes. J Mol Evol 1997, 44 (1), 66-73.
24. Dandekar, T.; Snel, B.; Huynen, M.; Bork, P., Conservation of gene order: a fingerprint of proteins that physically interact. Trends Biochem Sci 1998, 23 (9), 324-328.
25. Overbeek, R.; Fonstein, M.; D'Souza, M.; Pusch, G. D.; Maltsev, N., The use of gene clusters to infer functional coupling. Proc Natl Acad Sci U S A 1999, 96 (6), 2896-901.
26. Enright, A. J.; Iliopoulos, I.; Kyrpides, N. C; Ouzounis, C. A., Protein interaction maps for complete genomes based on gene fusion events. Nature 1999, 402 (6757), 86-90.
27. Ouzounis, C; Kyrpides, N., The emergence of major cellular processes in evolution. FEBS Lett 1996, 390 (2), 119-23.
28. Pellegrini, M.; Marcotte, E. M.; Thompson, M. J.; Eisenberg, D.; Yeates, T. O., Assigning protein functions by comparative genome analysis: protein phylogenetic profiles. Proc Natl Acad Sci U S A 1999, 96 (8), 4285-8.
29. Barker, D.; Pagel, M., Predicting functional gene links from phylo-genetic-statistical analyses of whole genomes. PLoS Comput Biol 2005, 1 (1), e3.
30. Najafabadi, H. S.; Salavati, R., Sequence-based prediction of protein-protein interactions by means of codon usage. Genome Biol 2008, 9 (5), R87.
31. Aloy, P.; Russell, R. B., Interrogating protein interaction networks through structural biology. Proceedings of the National Academy of Sciences 2002, 99 (9), 5896-5901.
32. Aloy, P.; Russell, R. B., InterPreTS: protein interaction prediction through tertiary structure. Bioinformatics 2003, 19 (1), 161-162.
33. Shoemaker, B. A.; Zhang, D.; Thangudu, R. R.; Tyagi, M.; Fong, J. H.; Marchler-Bauer, A.; Bryant, S. H.; Madej, T.; Panchenko, A. R., Inferred Biomolecular Interaction Server--a web server to analyze and predict protein interacting partners and binding sites. Nucleic acids research 2010, 38 (Database issue), D518-D524.
34. Lu, L.; Lu, H.; Skolnick, J., MULTIPROSPECTOR: an algorithm for the prediction of protein-protein interactions by multimeric threading. Proteins 2002, 49 (3), 350-64.
35. Rodriguez-Soca, Y.; Munteanu, C. R.; Dorado, J. N.; Pazos, A.; Prado-Prado, F. J.; González-Díaz, H., Trypano-PPI: A Web Server for Prediction of Unique Targets in Trypanosome Proteome by using Electrostatic Parameters of Protein-protein Interactions. Journal of Proteome Research 2009, 9 (2), 1182-1190.
36. Rodriguez-Soca, Y.; Munteanu, C. R.; Dorado, J.; Rabuñal, J.; Pazos, A.; González-Díaz, H., Plasmod-PPI: A web-server predicting complex biopolymer targets in plasmodium with entropy measures of protein-protein interactions. Polymer 2010, 51 (1), 264-273.
37. Sprinzak, E.; Margalit, H., Correlated sequence-signatures as markers of protein-protein interaction. J Mol Biol 2001, 311 (4), 681-92.
38. Deng, M.; Mehta, S.; Sun, F.; Chen, T., Inferring domain-domain interactions from protein-protein interactions. Genome Res 2002, 12 (10), 1540-8.
39. Morrison, J. L.; Breitling, R.; Higham, D. J.; Gilbert, D. R., A lock-and-key model for protein-protein interactions. Bioinformatics 2006, 22 (16), 2012-9.
40. Chen, X.-W.; Liu, M., Prediction of protein-protein interactions using random decision forest framework. Bioinformatics 2005, 21 (24), 4394-4400.
41. Wang, R.-S.; Wang, Y.; Wu, L.-Y.; Zhang, X.-S.; Chen, L., Analysis on multi-domain cooperation for predicting protein-protein interactions. BMC Bioinformatics 2007, 8 (1), 391.
42. Bock, J. R.; Gough, D. A., Predicting protein-protein interactions from primary structure. Bioinformatics 2001, 17 (5), 455-460.
43. Bock, J. R.; Gough, D. A., Whole-proteome interaction mining. Bioinformatics 2003, 19 (1), 125-134.
44. Shen, J.; Zhang, J.; Luo, X.; Zhu, W.; Yu, K.; Chen, K.; Li, Y.; Jiang, H., Predicting protein-protein interactions based only on sequences information. Proceedings of the National Academy of Sciences 2007, 104 (11), 4337-4341.
45. Aziz, M. M.; Maleki, M.; Rueda, L.; Raza, M.; Banerjee, S., Prediction of biological protein-protein interactions using atom-type and amino acid properties. Proteomics 2011, 11 (19), 3802-10.
46. Martin, S.; Roe, D.; Faulon, J.-L., Predicting protein-protein interactions using signature products. Bioinformatics 2005, 21 (2), 218-226.
47. Pitre, S.; Dehne, F.; Chan, A.; Cheetham, J.; Duong, A.; Emili, A.; Gebbia, M.; Greenblatt, J.; Jessulat, M.; Krogan, N.; Luo, X.; Gol-shani, A., PIPE: a protein-protein interaction prediction engine based on the re-occurring short polypeptide sequences between known interacting protein pairs. BMC Bioinformatics 2006, 7 (1), 365.
48. Nanni, L., Hyperplanes for predicting protein-protein interactions. Neurocomputing 2005, 69 (1-3), 257-263.
49. Nanni, L.; Lumini, A., An ensemble of K-local hyperplanes for predicting protein-protein interactions. Bioinformatics 2006, 22 (10), 1207-1210.
50. Guo, Y.; Yu, L.; Wen, Z.; Li, M., Using support vector machine combined with auto covariance to predict protein-protein interactions from protein sequences. Nucleic acids research 2008, 36 (9), 3025-3030.
51. Xia, J. F.; Han, K.; Huang, D. S., Sequence-based prediction of protein-protein interactions by means of rotation forest and autocorrelation descriptor. Protein Pept Lett 2010, 17 (1), 137-45.
52. Ben-Hur, A.; Noble, W. S., Kernel methods for predicting protein--protein interactions. Bioinformatics 2005, 21 (1), 38-46.
53. Rajasekaran, S.; Merlin, J. C.; Kundeti, V.; Mi, T.; Oommen, A.; Vyas, J.; Alaniz, I.; Chung, K.; Chowdhury, F.; Deverasatty, S.; Irvey, T. M.; Lacambacal, D.; Lara, D.; Panchangam, S.; Rathnay-ake, V.; Watts, P.; Schiller, M. R., A computational tool for identifying minimotifs in protein-protein interactions and improving the accuracy of minimotif predictions. Proteins 2011, 79 (1), 153-64.
54. Knisley, D.; Knisley, J., Predicting protein-protein interactions using graph invariants and a neural network. Computational Biology and Chemistry 2011, 35 (2), 108-113.
55. Zhang, Y.; Zhang, D.; Mi, G.; Ma, D.; Li, G.; Guo, Y.; Li, M.; Zhu, M., Using ensemble methods to deal with imbalanced data in predicting protein-protein interactions. Comput Biol Chem 2012, 36, 36-41.
56. Wu, X.; Zhu, L.; Guo, J.; Zhang, D. Y.; Lin, K., Prediction of yeast protein-protein interaction network: insights from the Gene Ontology and annotations. Nucleic acids research 2006, 34 (7), 2137-50.
57. Jain, S.; Bader, G. D., An improved method for scoring protein-protein interactions using semantic similarity within the gene ontology. BMC Bioinformatics 2010, 11, 562.
58. Maetschke, S. R.; Simonsen, M.; Davis, M. J.; Ragan, M. A., Gene Ontology-driven inference of protein-protein interactions using in-ducers. Bioinformatics 2012, 28 (1), 69-75.
59. Park, B.; Cui, G.; Lee, H.; Huang, D.-S.; Han, K., PPISearchEngine: gene ontology-based search for protein-protein interactions. Computer Methods in Biomechanics and Biomedical Engineering 2012, 1-8.
60. Blumenthal, T., Gene clusters and polycistronic transcription in eukaryotes. Bioessays 1998, 20 (6), 480-7.
61. Marcotte, E. M.; Pellegrini, M.; Ng, H. L.; Rice, D. W.; Yeates, T. O.; Eisenberg, D., Detecting protein function and protein-protein interactions from genome sequences. Science 1999, 285 (5428), 751-3.
62. Hue, M.; Riffle, M.; Vert, J. P.; Noble, W. S., Large-scale prediction of protein-protein interactions from structures. BMC Bioinfor-matics 2010, 11, 144.
63. Fernandez-Ballester, G.; Serrano, L., Prediction of protein-protein interaction based on structure. Methods Mol Biol 2006, 340, 207-34.
64. Krissinel, E.; Henrick, K., Inference of macromolecular assemblies from crystalline state. J Mol Biol 2007, 372 (3), 774-97.
65. Gibrat, J. F.; Madej, T.; Bryant, S. H., Surprising similarities in structure comparison. Curr Opin Struct Biol 1996, 6 (3), 377-85.
66. Berman, H. M.; Bhat, T. N.; Bourne, P. E.; Feng, Z.; Gilliland, G.; Weissig, H.; Westbrook, J., The Protein Data Bank and the challenge of structural genomics. Nat Struct Biol 2000, 7 Suppl, 957-9.
67. de Souza, S. J., Domain shuffling and the increasing complexity of biological networks. Bioessays 2012, n/a-n/a.
68. Terrapon, N.; Gascuel, O.; Marechal, E.; Brehelin, L., Fitting hidden Markov models of protein domains to a target species: application to Plasmodium falciparum. BMC Bioinformatics 2012, 13 (1), 67.
69. Richardson, J. S., The anatomy and taxonomy of protein structure. Adv Protein Chem 1981, 34, 167-339.
70. Punta, M.; Coggill, P. C.; Eberhardt, R. Y.; Mistry, J.; Tate, J.; Boursnell, C.; Pang, N.; Forslund, K.; Ceric, G.; Clements, J.; Heger, A.; Holm, L.; Sonnhammer, E. L. L.; Eddy, S. R.; Bateman, A.; Finn, R. D., The Pfam protein families database. Nucleic acids research 2012, 40 (D1), D290-D301.
71. Pagel, P.; Kovac, S.; Oesterheld, M.; Brauner, B.; Dunger-Kaltenbach, I.; Frishman, G.; Montrone, C.; Mark, P.; Stumpflen, V.; Mewes, H. W.; Ruepp, A.; Frishman, D., The MIPS mammalian protein-protein interaction database. Bioinformatics 2005, 21 (6), 832-4.
72. Chen, L.; Wu, L. Y.; Wang, Y.; Zhang, X. S., Inferring protein interactions from experimental data by association probabilistic method. Proteins 2006, 62 (4), 833-7.
73. Huang, C.; Morcos, F.; Kanaan, S. P.; Wuchty, S.; Chen, D. Z.; Izaguirre, J. A., Predicting protein-protein interactions from protein domains using a set cover approach. IEEE/ACM Trans Comput Biol Bioinform 2007, 4 (1), 78-87.
74. Vapnik, V. N., The nature of statistical learning theory. Springer-Verlag New York, Inc.: New York, NY, USA, 1995.
75. Manning, C. D.; Schütze, H., Foundations of Statistical Natural Language Processing. MIT Press: Cambridge, MA, USA, 1999.
76. Juan, J. R. g., Rotation Forest: A New Classifier Ensemble Method. IEEE Transactions on Pattern Analysis and Machine Intelligence 2006, 28, 1619-1630.
77. Moran, P. A., Notes on continuous stochastic phenomena. Bio-metrika 1950, 37 (1-2), 17-23.
78. Ashburner, M.; Ball, C. A.; Blake, J. A.; Botstein, D.; Butler, H.; Cherry, J. M.; Davis, A. P.; Dolinski, K.; Dwight, S. S.; Eppig, J. T.; Harris, M. A.; Hill, D. P.; Issel-Tarver, L.; Kasarskis, A.; Lewis, S.; Matese, J. C.; Richardson, J. E.; Ringwald, M.; Rubin, G. M.; Sherlock, G., Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nature genetics 2000, 25 (1), 25-9.
79. Obenauer, J. C.; Cantley, L. C.; Yaffe, M. B., Scansite 2.0: Pro-teome-wide prediction of cell signaling interactions using short sequence motifs. Nucleic acids research 2003, 31 (13), 3635-41.
80. Balla, S.; Thapar, V.; Verma, S.; Luong, T.; Faghri, T.; Huang, C. H.; Rajasekaran, S.; del Campo, J. J.; Shinn, J. H.; Mohler, W. A.; Maciejewski, M. W.; Gryk, M. R.; Piccirillo, B.; Schiller, S. R.; Schiller, M. R., Minimotif Miner: a tool for investigating protein function. Nature methods 2006, 3 (3), 175-7.
81. Rajasekaran, S.; Balla, S.; Gradie, P.; Gryk, M. R.; Kadaveru, K.; Kundeti, V.; Maciejewski, M. W.; Mi, T.; Rubino, N.; Vyas, J.; Schiller, M. R., Minimotif miner 2nd release: a database and web system for motif search. Nucleic acids research 2009, 37 (Database issue), D185-90.
82. Harris, B. Z.; Lim, W. A., Mechanisma and role of PDZ domains in signaling complex assembly. Journal of Cell Science 2001, 114 (18), 3219-3231.
83. Barrell, D.; Dimmer, E.; Huntley, R. P.; Binns, D.; O'Donovan, C.; Apweiler, R., The GOA database in 2009-an integrated Gene Ontology Annotation resource. Nucleic acids research 2009, 37 (suppl 1), D396-D403.
84. Dyer, M. D.; Murali, T. M.; Sobral, B. W., Computational prediction of host-pathogen protein-protein interactions. Bioinformatics 2007, 23 (13), i159-i166.
85. Davis, F. P.; Barkan, D. T.; Eswar, N.; McKerrow, J. H.; Sali, A., Host pathogen protein interactions predicted by comparative modeling. Protein science: a publication of the Protein Society 2007, 16 (12), 2585-96.
86. Lee, S. A.; Chan, C. H.; Tsai, C. H.; Lai, J. M.; Wang, F. S.; Kao, C. Y.; Huang, C. Y., Ortholog-based protein-protein interaction prediction and its application to inter-species interactions. BMC Bioinformatics 2008, 9 Suppl 12, S11.
87. Tastan, O.; Qi, Y.; Carbonell, J. G.; Klein-Seetharaman, J., Prediction of interactions between HIV-1 and human proteins by information integration. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing 2009, 516-27.
88. Itzhaki, Z., Domain-domain interactions underlying herpesvirus-human protein-protein interaction networks. PloS one 2011, 6 (7), e21724.
89. Tsao, T. T.-H.; Chan, C.-H.; Huang, C.-Y. F.; Lee, S.-A., The Prediction and Analysis of Inter-and Intra-Species Protein-Protein Interaction. In Systems and Computational Biology-Molecular and Cellular Experimental Systems, Yang, N.-S., Ed. InTech: 2011; p 322.
90. Bahir, I.; Fromer, M.; Prat, Y.; Linial, M., Viral adaptation to host: a proteome-based analysis of codon usage and amino acid preferences. Molecular systems biology 2009, 5, 311.
91. Mattson, M. P., Metal-catalyzed disruption of membrane protein and lipid signaling in the pathogenesis of neurodegenerative disorders. Annals of the New York Academy of Sciences 2004, 1012, 37-50.
92. Wuchty, S.; Almaas, E., Peeling the yeast protein network. Pro-teomics 2005, 5 (2), 444-9.
93. Jeong, H.; Mason, S. P.; Barabasi, A. L.; Oltvai, Z. N., Lethality and centrality in protein networks. Nature 2001, 411 (6833), 41-42.
94. Wachi, S.; Yoneda, K.; Wu, R., Interactome-transcriptome analysis reveals the high centrality of genes differentially expressed in lung cancer tissues. Bioinformatics 2005, 21 (23), 4205-4208.
95. Jonsson, P. F.; Bates, P. A., Global topological features of cancer proteins in the human interactome. Bioinformatics 2006, 22 (18), 2291-2297.
96. Goh, K.-I.; Cusick, M. E.; Valle, D.; Childs, B.; Vidal, M.; Ba-rabási, A.-L., The human disease network. Proceedings of the National Academy of Sciences 2007, 104 (21), 8685-8690.
97. Oti, M.; Snel, B.; Huynen, M. A.; Brunner, H. G., Predicting disease genes using protein-protein interactions. Journal of medical genetics 2006, 43 (8), 691-8.
98. Franke, L.; van Bakel, H.; Fokkens, L.; de Jong, E. D.; Egmont-Petersen, M.; Wijmenga, C., Reconstruction of a functional human gene network, with an application for prioritizing positional candidate genes. American journal of human genetics 2006, 78 (6), 1011-25.
99. Lage, K.; Karlberg, E. O.; Størling, Z. M.; Olason, P. I.; Pedersen, A. G.; Rigina, O.; Hinsby, A. M.; Tümer, Z.; Pociot, F.; Tomme-rup, N.; Moreau, Y.; Brunak, S., A human phenome-interactome network of protein complexes implicated in genetic disorders. Nature biotechnology 2007, 25 (3), 309-316.
100. Ideker, T.; Sharan, R., Protein networks in disease. Genome Res 2008, 18 (4), 644-52.
101. Goehler, H.; Lalowski, M.; Stelzl, U.; Waelter, S.; Stroedicke, M.; Worm, U.; Droege, A.; Lindenberg, K. S.; Knoblich, M.; Haenig, C.; Herbst, M.; Suopanki, J.; Scherzinger, E.; Abraham, C.; Bauer, B.; Hasenbank, R.; Fritzsche, A.; Ludewig, A. H.; Bussow, K.; Coleman, S. H.; Gutekunst, C. A.; Landwehrmeyer, B. G.; Le-hrach, H.; Wanker, E. E., A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease. Molecular cell 2004, 15 (6), 853-65.
102. Harding, A. E., The gene for Huntington's disease. BMJ (Clinical research ed.) 1993, 307 (6901), 396-397.
103. Lim, J.; Hao, T.; Shaw, C; Patel, A. J.; Szabó, G.; Rual, J.-F.; Fisk, C. J.; Li, N.; Smolyar, A.; Hill, D. E.; Barabási, A.-L.; Vidal, M.; Zoghbi, H. Y., A Protein Protein Interaction Network for Human Inherited Ataxias and Disorders of Purkinje Cell Degeneration. Cell 2006, 125 (4), 801-814.
104. Pujana, M. A.; Han, J. D.; Starita, L. M.; Stevens, K. N.; Tewari, M.; Ahn, J. S.; Rennert, G.; Moreno, V.; Kirchhoff, T.; Gold, B.; Assmann, V.; Elshamy, W. M.; Rual, J. F.; Levine, D.; Rozek, L. S.; Gelman, R. S.; Gunsalus, K. C; Greenberg, R. A.; Sobhian, B.; Bertin, N.; Venkatesan, K.; Ayivi-Guedehoussou, N.; Sole, X.; Hernandez, P.; Lazaro, C; Nathanson, K. L.; Weber, B. L.; Cusick, M. E.; Hill, D. E.; Offit, K.; Livingston, D. M.; Gruber, S. B.; Parvin, J. D.; Vidal, M., Network modeling links breast cancer susceptibility and centrosome dysfunction. Nature genetics 2007, 39 (11), 1338-49.
105. Lee, S.-A.; Tsao, T.; Yang, K.-C; Lin, H.; Kuo, Y.-L.; Hsu, C.-H.; Lee, W.-K.; Huang, K.-C; Kao, C.-Y., Construction and analysis of the protein-protein interaction networks for schizophrenia, bipolar disorder, and major depression. BMC Bioinformatics 2011, 12 (Suppl 13), S20.
106. Hyduke, D. R.; Jarboe, L. R.; Tran, L. M.; Chou, K. J. Y.; Liao, J. C, Integrated network analysis identifies nitric oxide response networks and dihydroxyacid dehydratase as a crucial target in Escherichia coli. Proceedings of the National Academy of Sciences 2007, 104 (20), 8484-8489.
107. Camargo, L. M.; Collura, V.; Rain, J. C; Mizuguchi, K.; Hermjakob, H.; Kerrien, S.; Bonnert, T. P.; Whiting, P. J.; Brandon, N. J., Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia. Molecular psychiatry 2007, 12 (1), 74-86.
108. Hwang, S.; Son, S. W.; Kim, S. C; Kim, Y. J.; Jeong, H.; Lee, D., A protein interaction network associated with asthma. Journal of theoretical biology 2008, 252 (4), 722-31.
109. Tanaka, T.; Oka, T.; Shimada, Y.; Umemoto, N.; Kuroyanagi, J.; Sakamoto, C; Zang, L.; Wang, Z.; Nishimura, Y., Pharmacoge-nomics of cardiovascular pharmacology: pharmacogenomic network of cardiovascular disease models. Journal of pharmacological sciences 2008, 107 (1), 8-14.
110. Chu, L. H.; Chen, B. S., Construction of a cancer-perturbed protein-protein interaction network for discovery of apoptosis drug targets. BMC systems biology 2008, 2, 56.
111. Fatumo, S.; Plaimas, K.; Mallm, J. P.; Schramm, G.; Adebiyi, E.; Oswald, M.; Eils, R.; Konig, R., Estimating novel potential drug targets of Plasmodium falciparum by analysing the metabolic network of knock-out strains in silico. Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 2009, 9 (3), 351-8.
112. Durmus Tekir, S.; Yalcin Arga, K.; Ulgen, K. O., Drug targets for tumorigenesis: insights from structural analysis of EGFR signaling network. Journal of biomedical informatics 2009, 42 (2), 228-36.
113. Berger, S. I.; Iyengar, R., Network analyses in systems pharmacology. Bioinformatics 2009, 25 (19), 2466-2472.
114. Ehrlich, P., Gesammelte Arbeiten. Springer-Verlag: Berlin, 1957.
115. Yildirim, M. A.; Goh, K. I.; Cusick, M. E.; Barabasi, A. L.; Vidal, M., Drug-target network. Nat Biotechnol 2007, 25 (10), 1119-26.
116. Ma'ayan, A.; Jenkins, S. L.; Goldfarb, J.; Iyengar, R., Network analysis of FDA approved drugs and their targets. The Mount Sinai journal of medicine, New York 2007, 74 (1), 27-32.
117. Nacher, J.; Schwartz, J.-M., A global view of drug-therapy interactions. BMC Pharmacology 2008, 8 (1), 5.
118. González-Díaz, H.; Prado-Prado, F.; García-Mera, X.; Alonso, N.; Abeijón, P.; Caamaño, O.; Yáñez, M.; Munteanu, C. R.; Pazos, A.; Dea-Ayuela, M. A. A.; Gómez-Muñoz, M. A. T.; Garijo, M. M.; Sansano, J.; Ubeira, F. M., MIND-BEST: Web Server for Drugs and Target Discovery; Design, Synthesis, and Assay of MAO-B Inhibitors and Theoretical-Experimental Study of G3PDH Protein from Trichomonas gallinae. Journal of Proteome Research 2010, 10 (4), 1698-1718.
119. González-Díaz, H.; Prado-Prado, F.; Sobarzo-Sánchez, E.; Haddad, M.; Maurel Chevalley, S.; Valentin, A.; Quetin-Leclercq, J.; Dea-Ayuela, M. A.; Teresa Gomez-Muños, M.; Munteanu, C. R.; José Torres-Labandeira, J.; García-Mera, X.; Tapia, R. A.; Ubeira, F. M., NL MIND-BEST: A web server for ligands and proteins discovery-Theoretic-experimental study of proteins of Giardia lam-blia and new compounds active against Plasmodium falciparum. Journal of theoretical biology 2011, 276 (1), 229-249.
120. Gonzalez-Diaz, H.; Prado-Prado, F.; Ubeira, F. M., Predicting antimicrobial drugs and targets with the MARCH-INSIDE approach. Current topics in medicinal chemistry 2008, 8 (18), 1676-90.
121. Hwang, W. C.; Zhang, A.; Ramanathan, M., Identification of information flow-modulating drug targets: a novel bridging paradigm for drug discovery. Clinical pharmacology and therapeutics 2008, 84 (5), 563-72.
122. Ruths, D. A.; Nakhleh, L.; Iyengar, M. S.; Reddy, S. A.; Ram, P. T., Hypothesis generation in signaling networks. Journal of computational biology: a journal of computational molecular cell biology 2006, 13 (9), 1546-57.
123. Dasika, M. S.; Burgard, A.; Maranas, C. D., A Computational Framework for the Topological Analysis and Targeted Disruption of Signal Transduction Networks. Biophysical Journal 2006, 91 (1), 382-398.
124. Singh, S.; Malik, B. K.; Sharma, D. K., Choke point analysis of metabolic pathways in E.histolytica: a computational approach for drug target identification. Bioinformation 2007, 2 (2), 68-72.
125. Sridhar, P.; Kahveci, T.; Ranka, S., An iterative algorithm for metabolic network-based drug target identification. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing 2007, 88-99.
126. Sridhar, P.; Song, B.; Kahveci, T.; Ranka, S., Mining metabolic networks for optimal drug targets. Pacific Symposium on Biocom-puting. Pacific Symposium on Biocomputing 2008, 291-302.
127. Altschul, S. F.; Madden, T. L.; Schaffer, 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 1997, 25 (17), 3389-402.
128. Stites, E. C.; Trampont, P. C.; Ma, Z.; Ravichandran, K. S., Network Analysis of Oncogenic Ras Activation in Cancer. Science 2007, 318 (5849), 463-467.
129. Zhao, S.; Li, S., Network-Based Relating Pharmacological and Genomic Spaces for Drug Target Identification. PloS one 2010, 5 (7), e11764.
130. Raman, M. P.; Singh, S.; Devi, P. R.; Velmurugan, D., Uncovering potential Drug Targets for Tuberculosis using Protein Networks. Bioinformation 2012, 8 (9), 403-6.
131. Szklarczyk, D.; Franceschini, A.; Kuhn, M.; Simonovic, M.; Roth, A.; Minguez, P.; Doerks, T.; Stark, M.; Muller, J.; Bork, P.; Jensen, L. J.; von Mering, C., The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic acids research 2011, 39 (Database issue), D561-8.
132. Wells, J. A.; McClendon, C. L., Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature 2007, 450 (7172), 1001-9.
133. Blundell, T. L.; Sibanda, B. L.; Montalvao, R. W.; Brewerton, S.; Chelliah, V.; Worth, C. L.; Harmer, N. J.; Davies, O.; Burke, D., Structural biology and bioinformatics in drug design: opportunities and challenges for target identification and lead discovery. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 2006, 361 (1467), 413-23.
134. Jubb, H.; Higueruelo, A. P.; Winter, A.; Blundell, T. L., Structural biology and drug discovery for protein-protein interactions. Trends in pharmacological sciences 2012, 33 (5), 241-8.
135. Spencer, R. W., High-throughput screening of historic collections: observations on file size, biological targets, and file diversity. Biotechnology and bioengineering 1998, 61 (1), 61-7.
136. Cochran, A. G., Antagonists of protein-protein interactions. Chemistry & biology 2000, 7 (4), R85-94.
137. Clackson, T.; Wells, J. A., A hot spot of binding energy in a hormone-receptor interface. Science 1995, 267 (5196), 383-6.
138. Bogan, A. A.; Thorn, K. S., Anatomy of hot spots in protein interfaces. J Mol Biol 1998, 280 (1), 1-9.
139. DeLano, W. L.; Ultsch, M. H.; de Vos, A. M., Wells, J. A., Convergent Solutions to Binding at a Protein-Protein Interface. Science 2000, 287 (5456), 1279-1283.
140. Pagliaro, L.; Felding, J.; Audouze, K.; Nielsen, S. J.; Terry, R. B.; Krog-Jensen, C.; Butcher, S., Emerging classes of protein-protein interaction inhibitors and new tools for their development. Current opinion in chemical biology 2004, 8 (4), 442-9.
141. Fry, D. C., Protein-protein interactions as targets for small molecule drug discovery. Biopolymers 2006, 84 (6), 535-52.
142. Higueruelo, A. P.; Schreyer, A.; Bickerton, G. R.; Pitt, W. R.; Groom, C. R.; Blundell, T. L., Atomic interactions and profile of small molecules disrupting protein-protein interfaces: the TIMBAL database. Chemical biology & drug design 2009, 74 (5), 457-67.
143. Kortemme, T.; Kim, D. E.; Baker, D., Computational alanine scanning of protein-protein interfaces. Science's STKE: signal trans-duction knowledge environment 2004, 2004 (219), pl2.
144. Camacho, C. J.; Zhang, C., FastContact: rapid estimate of contact and binding free energies. Bioinformatics 2005, 21 (10), 2534-6.
145. Lichtarge, O.; Bourne, H. R.; Cohen, F. E., An evolutionary trace method defines binding surfaces common to protein families. J Mol Biol 1996, 257 (2), 342-58.
146. Keskin, O.; Ma, B.; Nussinov, R., Hot regions in protein--protein interactions: the organization and contribution of structurally conserved hot spot residues. J Mol Biol 2005, 345 (5), 1281-94.
147. Ofran, Y.; Rost, B., Protein-protein interaction hotspots carved into sequences. PLoS Comput Biol 2007, 3 (7), e119.
148. Bromberg, Y.; Rost, B., Comprehensive in silico mutagenesis highlights functionally important residues in proteins. Bioinformat-ics 2008, 24 (16), i207-12.
149. Meireles, L. M.; Domling, A. S.; Camacho, C. J., ANCHOR: a web server and database for analysis of protein-protein interaction binding pockets for drug discovery. Nucleic acids research 2010, 38 (Web Server issue), W407-11.
150. Darnell, S. J.; Page, D.; Mitchell, J. C., An automated decision-tree approach to predicting protein interaction hot spots. Proteins 2007, 68 (4), 813-23.
151. Guney, E.; Tuncbag, N.; Keskin, O.; Gursoy, A., HotSprint: database of computational hot spots in protein interfaces. Nucleic acids research 2008, 36 (Database issue), D662-6.
152. Cho, K. I.; Kim, D.; Lee, D., A feature-based approach to modeling protein-protein interaction hot spots. Nucleic acids research 2009, 37 (8), 2672-87.
153. Tuncbag, N.; Gursoy, A.; Keskin, O., Identification of computational hot spots in protein interfaces: combining solvent accessibility and inter-residue potentials improves the accuracy. Bioinformat-ics 2009, 25 (12), 1513-20.
154. Lise, S.; Archambeau, C.; Pontil, M.; Jones, D. T., Prediction of hot spot residues at protein-protein interfaces by combining machine learning and energy-based methods. BMC Bioinformatics 2009, 10, 365.
155. Zhu, X.; Mitchell, J. C., KFC2: a knowledge-based hot spot prediction method based on interface solvation, atomic density, and plasticity features. Proteins 2011, 79 (9), 2671-83.
156. Koes, D. R.; Camacho, C. J., Small-molecule inhibitor starting points learned from protein-protein interaction inhibitor structure. Bioinformatics 2012, 28 (6), 784-91.
157. Rajamani, D.; Thiel, S.; Vajda, S.; Camacho, C. J., Anchor residues in protein-protein interactions. Proceedings of the National Academy of Sciences of the United States of America 2004, 101 (31), 11287-11292.
158. Liu, S.; Wu, S.; Jiang, S., HIV entry inhibitors targeting gp41: from polypeptides to small-molecule compounds. Current pharmaceutical design 2007, 13 (2), 143-62.
159. Christ, F.; Voet, A.; Marchand, A.; Nicolet, S.; Desimmie, B. A.; Marchand, D.; Bardiot, D.; Van der Veken, N. J.; Van Remoortel, B.; Strelkov, S. V.; De Maeyer, M.; Chaltin, P.; Debyser, Z., Rational design of small-molecule inhibitors of the LEDGF/p75-integrase interaction and HIV replication. Nature chemical biology 2010, 6 (6), 442-8.
160. Popowicz, G. M.; Dömling, A.; Holak, T. A., The Structure-Based Design of Mdm2/Mdmx-p53 Inhibitors Gets Serious. Angewandte Chemie International Edition 2011, 50 (12), 2680-2688.