Research Article
Hydrophobic complementarity in protein–protein docking
Alexander Berchanski,
Boaz Shapira,
Miriam Eisenstein,
Alexander Berchanski
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
A. Berchanski and B. Shapira contributed equally to this work.
Search for more papers by this authorBoaz Shapira
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
A. Berchanski and B. Shapira contributed equally to this work.
Search for more papers by this authorCorresponding Author
Miriam Eisenstein
Department of Chemical Services, Weizmann Institute of Science, Rehovot, Israel
Department of Chemical Services, The Weizmann Institute of Science, Rehovot 76100, Israel===Search for more papers by this authorAlexander Berchanski,
Boaz Shapira,
Miriam Eisenstein,
Alexander Berchanski
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
A. Berchanski and B. Shapira contributed equally to this work.
Search for more papers by this authorBoaz Shapira
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
A. Berchanski and B. Shapira contributed equally to this work.
Search for more papers by this authorCorresponding Author
Miriam Eisenstein
Department of Chemical Services, Weizmann Institute of Science, Rehovot, Israel
Department of Chemical Services, The Weizmann Institute of Science, Rehovot 76100, Israel===Search for more papers by this authorAbstract
Formation of hydrophobic contacts across a newly formed interface is energetically favorable. Based on this observation we developed a geometric–hydrophobic docking algorithm that estimates quantitatively the hydrophobic complementarity at protein–protein interfaces. Each molecule to be docked is represented as a grid of complex numbers, storing information regarding the shape of the molecule in the real part and information regarding the hydropathy of the surface in the imaginary part. The grid representations are correlated using fast Fourier transformations. The algorithm is used to compare the extent of hydrophobic complementarity in oligomers (represented by D2 tetramers) and in hetero-dimers of soluble proteins (complexes). We also test the implication of hydrophobic complementarity in distinguishing correct from false docking solutions. We find that hydrophobic complementarity at the interface exists in oligomers and in complexes, and in both groups the extent of such complementarity depends on the size of the interface. Thus, the non-polar portions of large interfaces are more often juxtaposed than non-polar portions of small interfaces. Next we find that hydrophobic complementarity helps to point out correct docking solutions. In oligomers it significantly improves the ranks of nearly correct reassembled and modeled tetramers. Combining geometric, electrostatic and hydrophobic complementarity for complexes gives excellent results, ranking a nearly correct solution < 10 for 5 of 23 tested systems, < 100 for 8 systems and < 1000 for 19 systems. Proteins 2004. © 2004 Wiley-Liss, Inc.
REFERENCES
- 1 Creighton TE. Protein structures and molecular properties. New York: W.H. Freeman, 1997.
- 2 Heifetz A, Katchalski-Katzir E, Eisenstein M. Electrostatics in protein–protein docking. Protein Sci 2002; 11: 571–587.
- 3 Argos P. An investigation of protein subunit and domain interfaces. Protein Eng 1988; 2: 101–113.
- 4 Janin J, Miller S, Chothia C. Surface, subunit interfaces and interior of oligomeric proteins. J Mol Biol 1988; 204: 155–164.
- 5 Jones S, Thornton JM. Principles of protein–protein interactions. Proc Natl Acad Sci USA 1996; 93: 13–20.
- 6 Lo Conte L, Chothia C, Janin J. The atomic structure of protein–protein recognition sites. J Mol Biol 1999; 285: 2177–2198.
- 7 Young L, Jernigan RL, Covell DG. A role for surface hydrophobicity in protein–protein recognition. Protein Sci 1994; 3: 717–729.
- 8 Miller S. The structure of interfaces between subunits of dimeric and tetrameric proteins. Protein Eng 1989; 3: 77–83.
- 9 Larsen TA, Olson AJ, Goodsell DS. Morphology of protein–protein interfaces. Structure 1998; 6: 421–427.
- 10
Glaser F,
Steinberg DM,
Vakser IA,
Ben-Tal N.
Residue frequencies and pairing preferences at protein–protein interfaces.
Proteins
2001;
43:
89–102.
10.1002/1097-0134(20010501)43:2<89::AID-PROT1021>3.0.CO;2-H CAS PubMed Web of Science® Google Scholar
- 11 Vakser IA, Aflalo C. Hydrophobic docking: a proposed enhancement to molecular recognition techniques. Proteins 1994; 20: 320–329.
- 12 Ackermann F, Herrmann G, Posch S, Sagerer G. Estimation and filtering of potential protein–protein docking positions. Bioinformatics 1998; 14: 196–205.
- 13 Chen R, Weng Z. Docking unbound proteins using shape complementarity, desolvation, and electrostatics. Proteins 2002; 47: 281–294.
- 14 Jackson RM, Gabb HA, Sternberg MJ. Rapid refinement of protein interfaces incorporating solvation: application to the docking problem. J Mol Biol 1998; 276: 265–285.
- 15
Palma PN,
Krippahl L,
Wampler JE,
Moura JJ.
BiGGER: a new (soft) docking algorithm for predicting protein interactions.
Proteins
2000;
39:
372–384.
10.1002/(SICI)1097-0134(20000601)39:4<372::AID-PROT100>3.0.CO;2-Q CAS PubMed Web of Science® Google Scholar
- 16 Katchalski-Katzir E, Shariv I, Eisenstein M, Friesem AA, Aflalo C, Vakser IA. Molecular surface recognition: determination of geometric fit between proteins and their ligands by correlation techniques. Proc Natl Acad Sci USA 1992; 89: 2195–2199.
- 17 Eisenstein M, Shariv I, Koren G, Friesem AA, Katchalski-Katzir E. Modeling supra-molecular helices: extension of the molecular surface recognition algorithm and application to the protein coat of the tobacco mosaic virus. J Mol Biol 1997; 266: 135–143.
- 18 Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Biol 1982; 157: 105–132.
- 19 Berchanski A, Eisenstein M. Construction of molecular assemblies via docking: modeling of tetramers with D2 Symmetry. Proteins 2003; 53: 817–829.
- 20 Berman HM, Westbrook J, Feng Z, et al. The Protein Data Bank. Nucleic Acids Res 2000; 28: 235–242.
- 21 Benning MM, Wesenberg G, Liu R, Taylor KL, Dunaway-Mariano D, Holden HM. The three-dimensional structure of 4-hydroxybenzoyl-CoA thioesterase from Pseudomonas sp. Strain CBS-3. J Biol Chem 1998; 273: 33572–33579.
- 22 Hohenester E, Keller JW, Jansonius JN. An alkali metal ion size-dependent switch in the active site structure of dialkylglycine decarboxylase. Biochemistry 1994; 33: 13561–13570.
- 23 Rafferty JB, Simon JW, Baldock C, et al. Common themes in redox chemistry emerge from the X-ray structure of oilseed rape (Brassica napus) enoyl acyl carrier protein reductase. Structure 1995; 3: 927–938.
- 24 Weeks CM, Roszak AW, Erman M, Kaiser R, Jornvall H, Ghosh D. Structure of rabbit liver fructose 1,6-bisphosphatase at 2.3 A resolution. Acta Crystallogr D Biol Crystallogr 1999; 55: 93–102.
- 25 Harrop SJ, Helliwell JR, Wan TCM, Kalb AJ, Tong L, Yariv J. Structure solution of a cubic crystal of concanavalin a complexed with methyl alpha-D-glucopyranoside. Acta Crystallogr D Biol Crystallogr 1996; 52: 143.
- 26 Fu Z, Hu Y, Konishi K, et al. Crystal structure of glycine N-methyltransferase from rat liver. Biochemistry 1996; 35: 11985–11993.
- 27 Ermler U, Merckel M, Thauer R, Shima S. Formylmethanofuran: tetrahydromethanopterin formyltransferase from Methanopyrus kandleri - new insights into salt-dependence and thermostability. Structure 1997; 5: 635–646.
- 28 Rigden DJ, Walter RA, Phillips SE, Fothergill-Gilmore LA. Polyanionic inhibitors of phosphoglycerate mutase: combined structural and biochemical analysis. J Mol Biol 1999; 289: 691–699.
- 29 Kim H, Hol WG. Crystal structure of Leishmania mexicana glycosomal glyceraldehyde-3- phosphate dehydrogenase in a new crystal form confirms the putative physiological active site structure. J Mol Biol 1998; 278: 5–11.
- 30 Singleton M, Isupov M, Littlechild J. X-ray structure of pyrrolidone carboxyl peptidase from the hyperthermophilic archaeon Thermococcus litoralis. Structure Fold Des 1999; 7: 237–244.
- 31 Blom N, Sygusch J. Product binding and role of the C-terminal region in class I D-fructose 1,6-bisphosphate aldolase. Nat Struct Biol 1997; 4: 36–39.
- 32 Schirmer T, Evans PR. Structural basis of the allosteric behaviour of phosphofructokinase. Nature 1990; 343: 140–145.
- 33 Zhang X, Chen L, Bancroft DP, Lai CK, Maione TE. Crystal structure of recombinant human platelet factor 4. Biochemistry 1994; 33: 8361–8366.
- 34 Korkhin Y, Kalb AJ, Peretz M, Bogin O, Burstein Y, Frolow F. NADP-dependent bacterial alcohol dehydrogenases: crystal structure, cofactor-binding and cofactor specificity of the ADHs of Clostridium beijerinckii and Thermoanaerobacter brockii. J Mol Biol 1998; 278: 967–981.
- 35 Ghosh D, Erman M, Wawrzak Z, Duax WL, Pangborn W. Mechanism of inhibition of 3 alpha, 20 beta-hydroxysteroid dehydrogenase by a licorice-derived steroidal inhibitor. Structure 1994; 2: 973–980.
- 36 Palm GJ, Lubkowski J, Derst C, Schleper S, Rohm KH, Wlodawer A. A covalently bound catalytic intermediate in Escherichia coli asparaginase: crystal structure of a Thr-89-Val mutant. FEBS Lett 1996; 390: 211–216.
- 37 Marquart M, Walter J, Deisenhofer J, Bode W, Huber R. The geometry of the reactive site and of the peptide groups in trypsin, trypsinogen and its complexes with inhibitors. Acta Crystallogr B 1983; 39: 480.
- 38 Walter J, Steigemann W, Singh TP, Bartunik H, Bode W, Huber A. New algorithm to model protein–protein recognition based on surface complementarity. Applications to antibody-antigen docking. J Mol Biol 1992; 228: 277–297.
- 39 Buckle AM, Henrick K, Fersht AR. Crystal structural analysis of mutations in the hydrophobic cores of barnase. J Mol Biol 1993; 234: 847–860.
- 40 Buckle AM, Schreiber G, Fersht AR. Protein–protein recognition: crystal structural analysis of a barnase- barstar complex at 2.0-Å resolution. Biochemistry 1994; 33: 8878–8889.
- 41 Lubienski MJ, Bycroft M, Freund SM, Fersht AR. Three-dimensional solution structure and 13C assignments of barstar using nuclear magnetic resonance spectroscopy. Biochemistry 1994; 33: 8866–8877.
- 42 McPhalen CA, James MN. Structural comparison of two serine proteinase-protein inhibitor complexes: eglin-c-subtilisin Carlsberg and CI-2-subtilisin Novo. Biochemistry 1988; 27: 6582–6598.
- 43 Fitzpatrick PA, Ringe D, Klibanov AM. X-ray crystal structure of cross-linked subtilisin Carlsberg in water vs. acetonitrile. Biochem Biophys Res Commun 1994; 198: 675–681.
- 44 Gros P, Fujinaga M, Dijkstra BW, Kalk KH, Hol WGJ. Crystallographic refinement by incorporation of molecular dynamics. The thermostable serine protease thermitase complexed with eglin-c. Acta Crystallogr B 1994; 45: 488–499.
- 45 Fujinaga M, Sielecki AR, Read RJ, Ardelt W, Laskowski M, James MN. Crystal and molecular structures of the complex of alpha-chymotrypsin with its inhibitor turkey ovomucoid third domain at 1.8 Å resolution. J Mol Biol 1987; 195: 397–418.
- 46 Papamokos E, Weber E, Bode W, et al. Crystallographic refinement of Japanese quail ovomucoid, a Kazal-type inhibitor, and model building studies of complexes with serine proteases. J Mol Biol 1982; 158: 515–537.
- 47 Blevins RA, Tulinsky A. The refinement and the structure of the dimer of alpha-chymotrypsin at 1.67-Å resolution. J Biol Chem 1985; 260: 4264–4275.
- 48 Huang Q, Wang Z, Li Y, Liu S, Tang Y. Refined 1.8 Å resolution crystal structure of the porcine epsilon- trypsin. Biochim Biophys Acta 1994; 1209: 77–82.
- 49 Song HK, Suh SW. Kunitz-type soybean trypsin inhibitor revisited: refined structure of its complex with porcine trypsin reveals an insight into the interaction between a homologous inhibitor from Erythrina caffra and tissue-type plasminogen activator. J Mol Biol 1998; 275: 347–363.
- 50 Teplyakov AV, Kuranova IP, Harutyunyan EH, et al. Crystal structure of thermitase at 1.4 Å resolution. J Mol Biol 1990; 214: 261–279.
- 51 van de Locht A, Bode W, Huber R, et al. The thrombin E192Q-BPTI complex reveals gross structural rearrangements: implications for the interaction with antithrombin and thrombomodulin. Embo J 1997; 16: 2977–2984.
- 52 Rydel TJ, Tulinsky A, Bode W, Huber R. Refined structure of the hirudin-thrombin complex. J Mol Biol 1991; 221: 583–601.
- 53 Harel M, Kleywegt GJ, Ravelli RB, Silman I, Sussman JL. Crystal structure of an acetylcholinesterase-fasciculin complex: interaction of a three-fingered toxin from snake venom with its target. Structure 1995; 3: 1355–1366.
- 54 Raves ML, Harel M, Pang YP, Silman I, Kozikowski AP, Sussman JL. Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A. Nat Struct Biol 1997; 4: 57–63.
- 55 LeDu MH, Housset D, Marchot P, Bougis PE, Navaza J, FontecillaCamps C. Structure of fasciculin 2 from green mamba snake venom: Evidence for unusual loop flexibility. Acta Crystallogr D Biol Crystallogr 1992; 52: 87.
- 56 Strynadka NC, Jensen SE, Alzari PM, James MN. A potent new mode of beta-lactamase inhibition revealed by the 1.7 Å X- ray crystallographic structure of the TEM-1-BLIP complex. Nat Struct Biol 1996; 3: 290–297.
- 57 Strynadka NC, Adachi H, Jensen SE, et al. Molecular structure of the acyl-enzyme intermediate in beta-lactam hydrolysis at 1.7 Å resolution. Nature 1992; 359: 700–705.
- 58 Strynadka NC, Jensen SE, Johns K, et al. Structural and kinetic characterization of a beta-lactamase-inhibitor protein. Nature 1994; 368: 657–660.
- 59 Padlan EA, Silverton EW, Sheriff S, Cohen GH, Smith-Gill SJ, Davies DR. Structure of an antibody-antigen complex: crystal structure of the HyHEL-10 Fab-lysozyme complex. Proc Natl Acad Sci USA 1989; 86: 5938–5942.
- 60 Maenaka K, Matsushima M, Song H, Sunada F, Watanabe K, Kumagai I. Dissection of protein-carbohydrate interactions in mutant hen egg-white lysozyme complexes and their hydrolytic activity. J Mol Biol 1995; 247: 281–293.
- 61 Cohen GH, Sheriff, S., Davies, D. R. Refined structure of the monoclonal antibody HyHEL-5 with its antigen hen egg-white lysozyme. Acta Crystallogr D Biol Crystallogr 1996; 52: 315.
- 62 Bhat TN, Bentley GA, Boulot G, et al. Bound water molecules and conformational stabilization help mediate an antigen-antibody association. Proc Natl Acad Sci USA 1994; 91: 1089–1093.
- 63 Prasad L, Waygood EB, Lee JS, Delbaere LT. The 2.5 Å resolution structure of the jel42 Fab fragment/HPr complex. J Mol Biol 1998; 280: 829–845.
- 64 Jia Z, Quail JW, Waygood EB, Delbaere LT. The 2.0-Å resolution structure of Escherichia coli histidine-containing phosphocarrier protein HPr. A redetermination. J Biol Chem 1993; 268: 22490–22501.
- 65 Braden BC, Fields BA, Ysern X, et al. Crystal structure of an Fv-Fv idiotope-anti-idiotope complex at 1.9 Å resolution. J Mol Biol 1996; 264: 137–151.
- 66 Huang M, Syed R, Stura EA, Stone MJ, Stefanko RS, Ruf W, Edgington TS, Wilson IA: The mechanism of an inhibitory antibody on TF-initiated blood coagulation revealed by the crystal structures of human tissue factor, Fab 5G9 and TF.G9 complex. J Mol Biol 1998; 275: 873–894.
- 67 Harlos K, Martin DM, O'Brien DP, Jones EY, Stuart DI, Polikarpov I, Miller A, Tuddenham EG, Boys CW: Crystal structure of the extracellular region of human tissue factor. Nature 1994; 370: 662–666.
- 68 Holmes MA, Buss TN, Foote J: Conformational correction mechanisms aiding antigen recognition by a humanized antibody. J Exp Med 1998; 187: 479–45.
- 69 Holmes MA, Foote J. Structural consequences of humanizing an antibody. J Immunol 1997; 158: 2192–2201.
- 70 Walsh MA, Schneider TR, Sieker LC, Dauter Z, Lamzin VS, Wilson KS: Refinement of triclinic hen egg-white lysozyme at atomic resolution. Acta Crystallogr D Biol Crystallogr 1998; 54: 522–546.
- 71 Li Y, Li H, Smith-Gill SJ, Mariuzza RA: Three-dimensional structures of the free and antigen-bound Fab from monoclonal antilysozyme antibody HyHEL-63(,). Biochemistry 2000; 39: 6296–6309.
- 72 Braden BC, Souchon H, Eisele JL, Bentley GA, Bhat TN, Navaza J, Poljak RJ: Three-dimensional structures of the free and the antigen-complexed Fab from monoclonal anti-lysozyme antibody D44.1. J Mol Biol 1994; 243: 767–781.
- 73 Mylvaganam SE, Paterson Y, Getzoff ED: Structural basis for the binding of an anti-cytochrome c antibody to its antigen: crystal structures of FabE8-cytochrome c complex to 1.8 Å resolution and FabE8 to 2.26 A resolution. J Mol Biol 1998; 281: 301–22.
- 74 Bushnell GW, Louie GV, Brayer GD: High-resolution three-dimensional structure of horse heart cytochrome c. J Mol Biol 1990; 214: 585–595
- 75 Arold S, Franken P, Strub MP, Hoh F, Benichou S, Benarous R, Dumas C: The crystal structure of HIV-1 Nef protein bound to the Fyn kinase SH3 domain suggests a role for this complex in altered T cell receptor signaling. Structure 1997; 5: 1361–1372.
- 76 Noble ME, Musacchio A, Saraste M, Courtneidge SA, Wierenga RK: Crystal structure of the SH3 domain in human Fyn; comparison of the three-dimensional structures of SH3 domains in tyrosine kinases and spectrin. Embo J 1993; 12: 2617–2624.
- 77 Scheffzek K, Ahmadian MR, Kabsch W, Wiesmuller L, Lautwein A, Schmitz F, Wittinghofer A: The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science 1997; 277: 333–338.
- 78 Scheffzek K, Lautwein A, Kabsch W, Ahmadian MR, Wittinghofer A: Crystal structure of the GTPase-activating domain of human p120GAP and implications for the interaction with Ras. Nature 1996; 384: 591–596.
- 79 Pai EF, Krengel U, Petsko GA, Goody RS, Kabsch W, Wittinghofer A: Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35 Å resolution: implications for the mechanism of GTP hydrolysis. Embo J 1990; 9: 2351–2359.
- 80 Chen L, Durley RC, Mathews FS, Davidson VL: Structure of an electron transfer complex: methylamine dehydrogenase, amicyanin, and cytochrome c551i. Science 1994; 264: 86–90.
- 81 Chen L, Doi M, Durley RC, Chistoserdov AY, Lidstrom ME, Davidson VL, Mathews FS: Refined crystal structure of methylamine dehydrogenase from Paracoccus denitrificans at 1.75 Å resolution. J Mol Biol 1998; 276: 131–149.
- 82 Durley R, Chen L, Lim LW, Mathews FS, Davidson VL: Crystal structure analysis of amicyanin and apoamicyanin from Paracoccus denitrificans at 2.0 Å and 1.8 Å resolution. Protein Sci 1993; 2: 739–752.
- 83 Welch M, Chinardet N, Mourey L, Birck C, Samama JP: Structure of the CheY-binding domain of histidine kinase CheA in complex with CheY. Nat Struct Biol 1998; 5: 25–29.
- 84 Bellsolell L, Prieto J, Serrano L, Coll M: Magnesium binding to the bacterial chemotaxis protein CheY results in large conformational changes involving its functional surface. J Mol Biol 1994; 238: 489–495.
- 85 Chen R, Mintseris J, Janin J, Weng Z: A protein–protein docking benchmark. Proteins 2003; 52: 88–91.
- 86 Hulsmeyer M, Hecht HJ, Niefind K, et al. Crystal structure of cis-biphenyl-2,3-dihydrodiol-2,3-dehydrogenase from a PCB degrader at 2.0 Å resolution. Protein Sci 1998; 7: 1286–1293.
- 87 Nakajima K, Yamashita A, Akama H, et al. Crystal structures of two tropinone reductases: different reaction stereospecificities in the same protein fold. Proc Natl Acad Sci USA 1998; 95: 4876–4881.
- 88 Schmidt M, Meier B, Parak F. X-ray structure of the cambialistic superoxide dismutase from Propionibacterium Shermanii active with Fe or Mn. J Biol Inorg Chem 1996; 1: 532.
- 89 Edwards RA, Baker HM, Whittaker MM, Whittaker JW, Jameson GB, Baker EN. Crystal structure of Escherichia coli manganese superoxide dismutase at 2.1-angstrom resolution. J Biol Inorg Chem 1998; 3: 161–165.
- 90 Munoz Dorado J, Arias JM. Protein kinases and phosphatases during the developmental cycle of myxobacteria. Microbiologia 1995; 11: 376–378.
- 91 Gonin P, Xu Y, Milon L, et al. Catalytic mechanism of nucleoside diphosphate kinase investigated using nucleotide analogues, viscosity effects, and X-ray crystallography. Biochemistry 1999; 38: 7265–7272.
- 92 Wodak SJ, Janin J. Structural basis of macromolecular recognition. Advances in Protein Chemistry 2003; 61: 9–73.
- 93 Tsai CJ, Xu D, Nussinov R: Structural motifs at protein–protein interfaces: protein cores versus two-state and three-state model complexes. Protein Sci 1997; 6: 1793–805.
Citing Literature
