Hot spots in protein-protein interfaces: Towards drug discovery

Progress in Biophysics and Molecular Biology

Volumn 116, Issue 2-3, 2014, Pages 165-173

  Cukuroglu, Engin ^a   Engin, H Billur ^a   Gursoy, Attila ^a   Keskin, Ozlem ^a  

^a KOÇ UNIVERSITY   (Turkey)

Author keywords

Drug design; Hot spot; Protein protein interaction; Protein protein interface

Indexed keywords

PROTEIN; PROTEIN BINDING;

BIOLOGY; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; GENETICS; HUMAN; METABOLISM; MUTATION; PROCEDURES; PROTEIN PROCESSING;

COMPUTATIONAL BIOLOGY; DRUG DISCOVERY; HUMANS; MUTATION; PROTEIN BINDING; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEINS;

EID: 84924028020     PISSN: 00796107     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.pbiomolbio.2014.06.003     Document Type: Article

References (112)

1. Acuner-Ozbabacan, S.E., Engin, H.B., Guven-Maiorov, E., Kuzu, G., Muratcioglu, S., Baspinar, A., Chen, Z., Van Waes, C., Gursoy, A., Keskin, O. and Nussinov, R. The Network of Interleukin-10 Protein Structural Interactions with Other Signaling Molecules and Its Implications in Inflammation and Cancer, BMC Genomics.
2. Acuner Ozbabacan S.E., Gursoy A., Nussinov R., Keskin O. The structural pathway of interleukin 1 (IL-1) initiated signaling reveals mechanisms of oncogenic mutations and SNPs in inflammation and cancer. PLoS Comput Biol. 2014, 10:e1003470.
3. Agius R., Torchala M., Moal I.H., Fernandez-Recio J., Bates P.A. Characterizing changes in the rate of protein-protein dissociation upon interface mutation using hotspot energy and organization. PLoS Comput Biol. 2013, 9:e1003216.
4. Arkin M.R., Randal M., DeLano W.L., Hyde J., Luong T.N., Oslob J.D., Raphael D.R., Taylor L., Wang J., McDowell R.S., Wells J.A., Braisted A.C. Binding of small molecules to an adaptive protein-protein interface. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:1603-1608.
5. Arkin M.R., Wells J.A. Small-molecule inhibitors of protein-protein interactions: progressing towards the dream. Nat. Rev. Drug. Discov. 2004, 3:301-317.
6. Armon A., Graur D., Ben-Tal N. ConSurf: an algorithmic tool for the identification of functional regions in proteins by surface mapping of phylogenetic information. J.Mol. Biol. 2001, 307:447-463.
7. Assi S.A., Tanaka T., Rabbitts T.H., Fernandez-Fuentes N. PCRPi: presaging critical residues in protein interfaces, a new computational tool to chart hot spots in protein interfaces. Nucleic Acids Res. 2010, 38:e86.
8. Barillari C., Marcou G., Rognan D. Hot-spots-guided receptor-based pharmacophores (HS-Pharm): a knowledge-based approach to identify ligand-anchoring atoms in protein cavities and prioritize structure-based pharmacophores. J.Chem. inf. Model. 2008, 48:1396-1410.
9. Basse M.J., Betzi S., Bourgeas R., Bouzidi S., Chetrit B., Hamon V., Morelli X., Roche P. 2P2Idb: a structural database dedicated to orthosteric modulation of protein-protein interactions. Nucleic acids Res. 2013, 41:D824-D827.
10. Berg T. Modulation of protein-protein interactions with small organic molecules. Angew. Chem. 2003, 42:2462-2481.
11. Berman H., Henrick K., Nakamura H., Markley J.L. The worldwide protein Data Bank (wwPDB): ensuring a single, uniform archive of PDB data. Nucleic Acids Res. 2007, 35:D301-D303.
12. 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 Res. 2000, 28:235-242.
13. Bogan A.A., Thorn K.S. Anatomy of hot spots in protein interfaces. J.Mol. Biol. 1998, 280:1-9.
14. Braisted A.C., Oslob J.D., Delano W.L., Hyde J., McDowell R.S., Waal N., Yu C., Arkin M.R., Raimundo B.C. Discovery of a potent small molecule IL-2 inhibitor through fragment assembly. J.Am. Chem. Soc. 2003, 125:3714-3715.
15. Cancer Genome Atlas Research, N, Weinstein J.N., Collisson E.A., Mills G.B., Shaw K.R., Ozenberger B.A., Ellrott K., Shmulevich I., Sander C., Stuart J.M. The Cancer genome atlas Pan-Cancer analysis project. Nat. Genet. 2013, 45:1113-1120.
16. Canner J.A., Sobo M., Ball S., Hutzen B., DeAngelis S., Willis W., Studebaker A.W., Ding K., Wang S., Yang D., Lin J. MI-63: a novel small-molecule inhibitor targets MDM2 and induces apoptosis in embryonal and alveolar rhabdomyosarcoma cells with wild-type p53. Br. J. Cancer 2009, 101:774-781.
17. Cesa L.C., Patury S., Komiyama T., Ahmad A., Zuiderweg E.R., Gestwicki J.E. Inhibitors of difficult protein-protein interactions identified by high-throughput screening of multiprotein complexes. ACS Chem. Biol. 2013, 8:1988-1997.
18. Cho K.I., Kim D., Lee D. Afeature-based approach to modeling protein-protein interaction hot spots. Nucleic Acids Res. 2009, 37:2672-2687.
19. Chung C.W., Coste H., White J.H., Mirguet O., Wilde J., Gosmini R.L., Delves C., Magny S.M., Woodward R., Hughes S.A., Boursier E.V., Flynn H., Bouillot A.M., Bamborough P., Brusq J.M., Gellibert F.J., Jones E.J., Riou A.M., Homes P., Martin S.L., Uings I.J., Toum J., Clement C.A., Boullay A.B., Grimley R.L., Blandel F.M., Prinjha R.K., Lee K., Kirilovsky J., Nicodeme E. Discovery and characterization of small molecule inhibitors of the BET family bromodomains. J.Med. Chem. 2011, 54:3827-3838.
20. Clackson T., Wells J.A. Ahot spot of binding energy in a hormone-receptor interface. Science 1995, 267:383-386.
21. Cukuroglu E., Gursoy A., Keskin O. Analysis of hot region organization in hub proteins. Ann. Biomed. Eng. 2010, 38:2068-2078.
22. Cukuroglu E., Gursoy A., Keskin O. HotRegion: a database of predicted hot spot clusters. Nucleic Acids Res. 2012, 40:D829-D833.
23. Cukuroglu E., Gursoy A., Nussinov R., Keskin O. Non-redundant unique interface structures as templates for modeling protein interactions. PLoS One 2014, 9:e86738.
24. Darnell S.J., Page D., Mitchell J.C. An automated decision-tree approach to predicting protein interaction hot spots. Proteins 2007, 68:813-823.
25. David A., Razali R., Wass M.N., Sternberg M.J. Protein-protein interaction sites are hot spots for disease-associated nonsynonymous SNPs. Hum. Mutat. 2012, 33:359-363.
26. del Sol A., O'Meara P. Small-world network approach to identify key residues in protein-protein interaction. Proteins 2005, 58:672-682.
27. DeLano W.L. Unraveling hot spots in binding interfaces: progress and challenges. Curr. Opin. Struct. biol. 2002, 12:14-20.
28. Domling A. Small molecular weight protein-protein interaction antagonists: an insurmountable challenge?. Curr. Opin. Chem. biol. 2008, 12:281-291.
29. Emami K.H., Nguyen C., Ma H., Kim D.H., Jeong K.W., Eguchi M., Moon R.T., Teo J.L., Kim H.Y., Moon S.H., Ha J.R., Kahn M. Asmall molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected]. Proc. Natl. Acad. Sci. U. S. A 2004, 101:12682-12687.
30. Engin H.B., Guney E., Keskin O., Oliva B., Gursoy A. Integrating structure to protein-protein interaction networks that drive metastasis to brain and lung in breast cancer. PLoS One 2013, 8:e81035.
31. Engin H.B., Gursoy A., Nussinov R., Keskin O. Network-based strategies can help mono- and poly-pharmacology drug discovery: a systems biology view. Curr Pharm Des 2014, 20:1201-1207.
32. English A.C., Done S.H., Caves L.S., Groom C.R., Hubbard R.E. Locating interaction sites on proteins: the crystal structure of thermolysin soaked in 2% to 100% isopropanol. Proteins 1999, 37:628-640.
33. Fernández-Recio J. Prediction of protein binding sites and hot spots. WIREs Comput Mol. Sci. 2011, 1:18.
34. Filippakopoulos P., Qi J., Picaud S., Shen Y., Smith W.B., Fedorov O., Morse E.M., Keates T., Hickman T.T., Felletar I., Philpott M., Munro S., McKeown M.R., Wang Y., Christie A.L., West N., Cameron M.J., Schwartz B., Heightman T.D., La Thangue N., French C.A., Wiest O., Kung A.L., Knapp S., Bradner J.E. Selective inhibition of BET bromodomains. Nature 2010, 468:1067-1073.
35. Fischer T.B., Arunachalam K.V., Bailey D., Mangual V., Bakhru S., Russo R., Huang D., Paczkowski M., Lalchandani V., Ramachandra C., Ellison B., Galer S., Shapley J., Fuentes E., Tsai J. The binding interface database (BID): a compilation of amino acid hot spots in protein interfaces. Bioinformatics 2003, 19:1453-1454.
36. Fleishman S.J., Whitehead T.A., Ekiert D.C., Dreyfus C., Corn J.E., Strauch E.M., Wilson I.A., Baker D. Computational design of proteins targeting the conserved stem region of influenza hemagglutinin. Science 2011, 332:816-821.
37. Fry D.C. Protein-protein interactions as targets for small molecule drug discovery. Biopolymers 2006, 84:535-552.
38. Fry D.C. Small-molecule inhibitors of protein-protein interactions: how to mimic a protein partner. Curr. Pharm. Des. 2012, 18:4679-4684.
39. Gao Y., Wang R., Lai L. Structure-based method for analyzing protein-protein interfaces. J.Mol. Model 2004, 10:44-54.
40. Genomes Project C., Abecasis G.R., Auton A., Brooks L.D., DePristo M.A., Durbin R.M., Handsaker R.E., Kang H.M., Marth G.T., McVean G.A. An integrated map of genetic variation from 1092 human genomes. Nature 2012, 491:56-65.
41. Geppert T., Hoy B., Wessler S., Schneider G. Context-based identification of protein-protein interfaces and "hot-spot" residues. Chem. Biol. 2011, 18:344-353.
42. Gonzalez-Ruiz D., Gohlke H. Targeting protein-protein interactions with small molecules: challenges and perspectives for computational binding epitope detection and ligand finding. Curr. Med. Chem. 2006, 13:2607-2625.
43. Grosdidier S., Fernandez-Recio J. Identification of hot-spot residues in protein-protein interactions by computational docking. BMC Bioinfo. 2008, 9:447.
44. Guerois R., Nielsen J.E., Serrano L. Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations. J.Mol. Biol. 2002, 320:369-387.
45. Guharoy M., Chakrabarti P. Conservation and relative importance of residues across protein-protein interfaces. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:15447-15452.
46. Guney E., Tuncbag N., Keskin O., Gursoy A. HotSprint: database of computational hot spots in protein interfaces. Nucleic Acids Res. 2008, 36:D662-D666.
47. Hajduk P.J., Huth J.R., Fesik S.W. Druggability indices for protein targets derived from NMR-based screening data. J.Med. Chem. 2005, 48:2518-2525.
48. Haliloglu T., Erman B. Analysis of correlations between energy and residue fluctuations in native proteins and determination of specific sites for binding. Phys. Rev. Lett. 2009, 102:088103.
49. Hall D.R., Ngan C.H., Zerbe B.S., Kozakov D., Vajda S. Hot spot analysis for driving the development of hits into leads in fragment-based drug discovery. J.Chem. inf. Model. 2012, 52:199-209.
50. Hopkins A.L., Groom C.R. The druggable genome. Nat. Rev. Drug. Discov. 2002, 1:727-730.
51. Hsu C.M., Chen C.Y., Liu B.J., Huang C.C., Laio M.H., Lin C.C., Wu T.L. Identification of hot regions in protein-protein interactions by sequential pattern mining. BMC Bioinforma. 2007, 8(Suppl.5):S8.
52. Humphrey W., Dalke A., Schulten K. VMD: visual molecular dynamics. J.Mol. Graph 1996, 14. 33-38, 27-28.
53. Huo S., Massova I., Kollman P.A. Computational alanine scanning of the 1:1 human growth hormone-receptor complex. J.Comput Chem. 2002, 23:15-27.
54. International HapMap C., Altshuler D.M., Gibbs R.A., Peltonen L., Altshuler D.M., Gibbs R.A., Peltonen L., Dermitzakis E., Schaffner S.F., Yu F., Peltonen L., Dermitzakis E., Bonnen P.E., Altshuler D.M., Gibbs R.A., de Bakker P.I., Deloukas P., Gabriel S.B., Gwilliam R., Hunt S., Inouye M., Jia X., Palotie A., Parkin M., Whittaker P., Yu F., Chang K., Hawes A., Lewis L.R., Ren Y., Wheeler D., Gibbs R.A., Muzny D.M., Barnes C., Darvishi K., Hurles M., Korn J.M., Kristiansson K., Lee C., McCarrol S.A., Nemesh J., Dermitzakis E., Keinan A., Montgomery S.B., Pollack S., Price A.L., Soranzo N., Bonnen P.E., Gibbs R.A., Gonzaga-Jauregui C., Keinan A., Price A.L., Yu F., Anttila V., Brodeur W., Daly M.J., Leslie S., McVean G., Moutsianas L., Nguyen H., Schaffner S.F., Zhang Q., Ghori M.J., McGinnis R., McLaren W., Pollack S., Price A.L., Schaffner S.F., Takeuchi F., Grossman S.R., Shlyakhter I., Hostetter E.B., Sabeti P.C., Adebamowo C.A., Foster M.W., Gordon D.R., Licinio J., Manca M.C., Marshall P.A., Matsuda I., Ngare D., Wang V.O., Reddy D., Rotimi C.N., Royal C.D., Sharp R.R., Zeng C., Brooks L.D., McEwen J.E. Integrating common and rare genetic variation in diverse human populations. Nature 2010, 467:52-58.
55. Jubb H., Higueruelo A.P., Winter A., Blundell T.L. Structural biology and drug discovery for protein-protein interactions. Trends Pharmacol. Sci. 2012, 33:241-248.
56. Kar G., Kuzu G., Keskin O., Gursoy A. Protein-protein interfaces integrated into interaction networks: implications on drug design. Curr. Pharm. Des. 2012, 18:4697-4705.
57. 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, 345:1281-1294.
58. Keskin O., Nussinov R. Similar binding sites and different partners: implications to shared proteins in cellular pathways. Structure 2007, 15:341-354.
59. Kim P.M., Lu L.J., Xia Y., Gerstein M.B. Relating three-dimensional structures to protein networks provides evolutionary insights. Science 2006, 314:1938-1941.
60. Koes D.R., Camacho C.J. Small-molecule inhibitor starting points learned from protein-protein interaction inhibitor structure. Bioinformatics 2012, 28:784-791.
61. Kortemme T., Baker D. Asimple physical model for binding energy hot spots in protein-protein complexes. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:14116-14121.
62. Kortemme T., Kim D.E., Baker D. Computational alanine scanning of protein-protein interfaces. Sci. STKE 2004, 2004:l2.
63. Kozakov D., Hall D.R., Chuang G.Y., Cencic R., Brenke R., Grove L.E., Beglov D., Pelletier J., Whitty A., Vajda S. Structural conservation of druggable hot spots in protein-protein interfaces. Proc. Natl. Acad. Sci. U. S. A 2011, 108:13528-13533.
64. Kruger D.M., Gohlke H. DrugScorePPI webserver: fast and accurate in silico alanine scanning for scoring protein-protein interactions. Nucleic Acids Res. 2010, 38:W480-W486.
65. Landon M.R., Lancia D.R., Yu J., Thiel S.C., Vajda S. Identification of hot spots within druggable binding regions by computational solvent mapping of proteins. J.Med. Chem. 2007, 50:1231-1240.
66. Li H., Liu A., Zhao Z., Xu Y., Lin J., Jou D., Li C. Fragment-based drug design and drug repositioning using multiple ligand simultaneous docking (MLSD): identifying celecoxib and template compounds as novel inhibitors of signal transducer and activator of transcription 3 (STAT3). J.Med. Chem. 2011, 54:5592-5596.
67. Li J., Liu Q. 'Double water exclusion': a hypothesis refining the O-ring theory for the hot spots at protein interfaces. Bioinformatics 2009, 25:743-750.
68. Li X., Keskin O., Ma B., Nussinov R., Liang J. Protein-protein interactions: hot spots and structurally conserved residues often locate in complemented pockets that pre-organized in the unbound states: implications for docking. J.Mol. Biol. 2004, 344:781-795.
69. Liang S., Liu Z., Li W., Ni L., Lai L. Construction of protein binding sites in scaffold structures. Biopolymers 2000, 54:515-523.
70. Liepinsh E., Otting G. Organic solvents identify specific ligand binding sites on protein surfaces. Nat. Biotechnol. 1997, 15:264-268.
71. 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 Bioinforma. 2009, 10:365.
72. Lise S., Buchan D., Pontil M., Jones D.T. Predictions of hot spot residues at protein-protein interfaces using support vector machines. PLoS One 2011, 6:e16774.
73. Liu S., Zhu X., Liang H., Cao A., Chang Z., Lai L. Nonnatural protein-protein interaction-pair design by key residues grafting. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:5330-5335.
74. London N., Raveh B., Schueler-Furman O. Druggable protein-protein interactions - from hot spots to hot segments. Curr. Opin. Chem. biol. 2013, 17:952-959.
75. Ma B., Nussinov R. Druggable orthosteric and allosteric hot spots to target protein-protein interactions. Curr. Pharm. Des. 2014, 20:1293-1301.
76. Mattos C., Ringe D. Locating and characterizing binding sites on proteins. Nat. Biotechnol. 1996, 14:595-599.
77. Meenan N.A., Sharma A., Fleishman S.J., Macdonald C.J., Morel B., Boetzel R., Moore G.R., Baker D., Kleanthous C. The structural and energetic basis for high selectivity in a high-affinity protein-protein interaction. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:10080-10085.
78. Moreira I.S., Fernandes P.A., Ramos M.J. Computational alanine scanning mutagenesis-an improved methodological approach. J.Comput Chem. 2007, 28:644-654.
79. Moreira I.S., Fernandes P.A., Ramos M.J. Hot spots-a review of the protein-protein interface determinant amino-acid residues. Proteins 2007, 68:803-812.
80. Nicodeme E., Jeffrey K.L., Schaefer U., Beinke S., Dewell S., Chung C.W., Chandwani R., Marazzi I., Wilson P., Coste H., White J., Kirilovsky J., Rice C.M., Lora J.M., Prinjha R.K., Lee K., Tarakhovsky A. Suppression of inflammation by a synthetic histone mimic. Nature 2010, 468:1119-1123.
81. Nishi H., Hashimoto K., Panchenko A.R. Phosphorylation in protein-protein binding: effect on stability and function. Structure 2011, 19:1807-1815.
82. Nussinov R., Tsai C.J., Xin F., Radivojac P. Allosteric post-translational modification codes. Trends Biochem Sci. 2012, 37:447-455.
83. Ofran Y., Rost B. Protein-protein interaction hotspots carved into sequences. PLoS Comput Biol. 2007, 3:e119.
84. Ozbek P., Soner S., Haliloglu T. Hot spots in a network of functional sites. PLoS One 2013, 8:e74320.
85. Pavelka A., Chovancova E., Damborsky J. HotSpot Wizard: a web server for identification of hot spots in protein engineering. Nucleic Acids Res. 2009, 37:W376-W383.
86. Rajamani D., Thiel S., Vajda S., Camacho C.J. Anchor residues in protein-protein interactions. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:11287-11292.
87. Reichmann D., Rahat O., Albeck S., Meged R., Dym O., Schreiber G. The modular architecture of protein-protein binding interfaces. Proc. Natl. Acad. Sci. U. S. A 2005, 102:57-62.
88. Schaller M.D., Parsons J.T. pp125FAK-dependent tyrosine phosphorylation of paxillin creates a high-affinity binding site for Crk. Mol. Cell. Biol. 1995, 15:2635-2645.
89. Schiro M.M., Stauber S.E., Peterson T.L., Krueger C., Darnell S.J., Satyshur K.A., Drinkwater N.R., Newton M.A., Hoffmann F.M. Mutations in protein-binding hot-spots on the hub protein Smad3 differentially affect its protein interactions and Smad3-regulated gene expression. PLoS One 2011, 6:e25021.
90. Schuster-Bockler B., Bateman A. Protein interactions in human genetic diseases. Genome Biol. 2008, 9:R9.
91. Seco J., Luque F.J., Barril X. Binding site detection and druggability index from first principles. J.Med. Chem. 2009, 52:2363-2371.
92. Shulman-Peleg A., Shatsky M., Nussinov R., Wolfson H.J. Spatial chemical conservation of hot spot interactions in protein-protein complexes. BMC Biol. 2007, 5:43.
93. Straub C.S. Targeting IAPs as an approach to anti-cancer therapy. Curr. Top. Med. Chem. 2011, 11:291-316.
94. Thangudu R.R., Bryant S.H., Panchenko A.R., Madej T. Modulating protein-protein interactions with small molecules: the importance of binding hotspots. J.Mol. Biol. 2012, 415:443-453.
95. Thorn K.S., Bogan A.A. ASEdb: a database of alanine mutations and their effects on the free energy of binding in protein interactions. Bioinformatics 2001, 17:284-285.
96. Tse C., Shoemaker A.R., Adickes J., Anderson M.G., Chen J., Jin S., Johnson E.F., Marsh K.C., Mitten M.J., Nimmer P., Roberts L., Tahir S.K., Xiao Y., Yang X., Zhang H., Fesik S., Rosenberg S.H., Elmore S.W. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008, 68:3421-3428.
97. Tuncbag N., Gursoy A., Keskin O. Identification of computational hot spots in protein interfaces: combining solvent accessibility and inter-residue potentials improves the accuracy. Bioinformatics 2009, 25:1513-1520.
98. Tuncbag N., Keskin O., Gursoy A. HotPoint: hot spot prediction server for protein interfaces. Nucleic acids Res. 2010, 38:W402-W406.
99. Tuncbag N., Salman F.S., Keskin O., Gursoy A. Analysis and network representation of hotspots in protein interfaces using minimum cut trees. Proteins 2010, 78:2283-2294.
100. Villoutreix B.O., Labbe C.M., Lagorce D., Laconde G., Sperandio O. Aleap into the chemical space of protein-protein interaction inhibitors. Curr. Pharm. Des. 2012, 18:4648-4667.
101. Vu B.T., Vassilev L. Small-molecule inhibitors of the p53-MDM2 interaction. Curr. Top. Microbiol. Immunol. 2011, 348:151-172.
102. Wang L., Hou Y., Quan H., Xu W., Bao Y., Li Y., Fu Y., Zou S. Acompound-based computational approach for the accurate determination of hot spots. Protein Sci. 2013, 22:1060-1070.
103. Wang L., Liu Z.P., Zhang X.S., Chen L. Prediction of hot spots in protein interfaces using a random forest model with hybrid features. Protein Eng. Des. Sel. 2012, 25:119-126.
104. Wang X., Wei X., Thijssen B., Das J., Lipkin S.M., Yu H. Three-dimensional reconstruction of protein networks provides insight into human genetic disease. Nat. Biotechnol. 2012, 30:159-164.
105. Wells J.A., McClendon C.L. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature 2007, 450:1001-1009.
106. Xia J.F., Zhao X.M., Song J., Huang D.S. APIS: accurate prediction of hot spots in protein interfaces by combining protrusion index with solvent accessibility. BMC Bioinforma. 2010, 11:174.
107. Yogurtcu O.N., Erdemli S.B., Nussinov R., Turkay M., Keskin O. Restricted mobility of conserved residues in protein-protein interfaces in molecular simulations. Biophys. J. 2008, 94:3475-3485.
108. Zerbe B.S., Hall D.R., Vajda S., Whitty A., Kozakov D. Relationship between hot spot residues and ligand binding hot spots in protein-protein interfaces. J.Chem. inf. Model. 2012, 52:2236-2244.
109. Zhang C., Lai L. Towards structure-based protein drug design. Biochem. Soc. Trans. 2011, 39(Suppl.1):1382-1386. following 1386.
110. Zhang C., Lai L. AutoMatch: target-binding protein design and enzyme design by automatic pinpointing potential active sites in available protein scaffolds. Proteins 2012, 80:1078-1094.
111. Zhong Q., Simonis N., Li Q.R., Charloteaux B., Heuze F., Klitgord N., Tam S., Yu H., Venkatesan K., Mou D., Swearingen V., Yildirim M.A., Yan H., Dricot A., Szeto D., Lin C., Hao T., Fan C., Milstein S., Dupuy D., Brasseur R., Hill D.E., Cusick M.E., Vidal M. Edgetic perturbation models of human inherited disorders. Mol. Syst. Biol. 2009, 5:321.
112. Zhu X., Mitchell J.C. KFC2: a knowledge-based hot spot prediction method based on interface solvation, atomic density, and plasticity features. Proteins 2011, 79:2671-2683.