Predicting, modelling and understanding biomolecular interactions in the post-genomic era


With the presently available amount of genetic information a central question arises: how do the various biomolecular units work together to fulfil their tasks? To answer this question, structural information on proteins and their interactions with other biomolecules is required. Gaining molecular insight into interactions will also greatly impact drug development programs. Considering the huge number of protein-protein interactions, their often weak and transient nature and the limitations of traditional structure determination methods, fast and reliable bioinformatic and computational methods are needed.

Our main objective is to develop reliable bioinformatic and computational approaches to predict, model and dissect biomolecular interactions at an atomic level. For this, bioinformatic data such as sequence conservation and structural information will be combined with available biochemical or biophysical experimental data to drive the modelling process. The advantages of this approach over conventional structural techniques are the speed-up and the possibility to study complexes that can not (or only with considerable effort) be studied otherwise. As a model system we will study E2-E3 interactions along the ubiquitination pathway, mutations in which can cause human diseases like cancer, Parkinson's and cardiovascular diseases. The bioinformatic and modelling efforts will benefit from ongoing proteomic studies of E2-E3 interactions within the ABC cluster in Utrecht, allowing us to validate and refine our computational methods. Predicting the specificity of E2-E3 interactions will, together with structural information, enable development of class-specific drugs against medically-relevant E2-E3 complexes.

In this project, computational modelling, bioinformatic and experimental data will be coupled in an original, innovative and synergistic manner. This will open the route to systematic and genome-wide studies of protein interactions. We will develop for this purpose a server that can predict atomic structures of biomolecular complexes using bioinformatic and proteomics data. It will be externally accessible, making it invaluable for molecular interactome analysis.

Keywords: biomolecular complexes; interactions; bioinformatics; docking; ubiquitination



  • M. Krzeminski(2009): Intrinsic disorder in biomolecular systems. A modelling Challenge  27 november 2009
  • S.J. de Vries(2009): How Proteins Get in Touch  3 juni 2009
  • P.L. Kastritis(2012): On the binding affinity of macromolecular complexes. , Utrecht  17 december 2012
  • E. Karaca(2014): Dissecting Biomolecular Interactions by Integrative Modeling. , Utrecht  6 februari 2013

Hoofdstuk in boek

  • A.D.J. van Dijk, A.M.J.J. Bonvin, G. Fuentes, A. Kukol(2008): Methods in Molecular Biology 443 pp. 175 - 186
  • AMJJ Bonvin, M Zacharrias, ASJ Melquiond(2010): Protein-protein complexes: analysis, modelling and drug design pp. 183 - 209 , London
  • P.L. Kastritis, A.D.J. van Dijk, A.M.J.J. Bonvin(2012): Methods in Molecular Biology pp. 355 - 374 , New-York
  • P.L. Kastritis, A.M.J.J. Bonvin(2012): Antimicrobial Drug Discovery. Emerging Strategies pp. 232 - 246 , Oxfordshire UK
  • C. Schmitz, A.S.J. Melquiond, S.J. de Vries, E. Karaca, M. van Dijk, P.L. Kastritis, A.M.J.J. Bonvin(2012): NMR in Mechanistic Systems Biology pp. 512 - 535 , Weinheim, Germany
  • D. Kihara, G.C.P. van Zundert, A.M.J.J. Bonvin(2014): Methods in Molecular Biology pp. 163 - 179 , New York

Wetenschappelijk artikel

  • C.G. Kalodimos, D. Keramisanou, I. Gelis, A.M.J.J. Bonvin(2007): Signal sequence recognition by the translocase motor SecA studied by NMR Cell pp. 756 - 769
  • S Karamanou, CG Kalodimos, G Gouridis, I. Gellis, M Koukaki, D Keramisanou, A.M.J.J. Bonvin, A. Economou(2007): Structural basis for signal sequence recognition by the translocase motor SecA determined by NMR. Cell pp. 756 - 759
  • A.D.J. van Dijk, A.M.J.J. Bonvin, V. Hsu, A. Thureau, S.J. de Vries, T. Wassenaar, M. Krzeminski, M. van Dijk(2007): HADDOCK versus HADDOCK: New features and performance of HADDOCK2.0 on the CAPRI targets Proteins: Struc. Funct. & Bioinformatic pp. 726 - 733
  • A.M.J.J. Bonvin, H.C. Siebert, A.M. Wu, M. Krzeminski, H-J. Gabius, S. André, J.-H. Liu, T. Singh, R. Russwurm(2007): Activity-structure correlations in divergent lectin-evolution: fine specificity of chicken galectin CG-14 and computational analysis of flexible ligand docking for CG-14 and the closely related CG-16. Glycobiology pp. 165 - 184
  • M. Assfalg, L. Ragona, S. Tomaselli, P. Ferranti, A.M.J.J. Bonvin, R. Longhi, L. Zetta, H. Molinari(2007): NMR-based modeling and binding studies of a ternary complex between chicken liver bile acid binding protein and bile acids. Proteins: Struc. Funct. & Bioinformatic pp. 177 - 191
  • R. Kopke Salinas, A.M.J.J. Bonvin, C.S. Farah, F. Correa-Victoria(2008): Deciphering the role of the electrostatic interactions in the a-Tropomyosin head-to-tail complex. Proteins: Struc. Funct. & Bioinformatic pp. 902 - 917
  • B. de Kruiff, A.M. Verel, W.T.M. Jansen, R.M.J. Liskamp, R.J. Pieters, A.M.J.J. Bonvin, C.J. Arnusch, E. Breukink(2008): Vancomycin-nisin(1-12) conjugate restores activity against vancomycin resistant enterococci (VRE). Biochemistry pp. 12661 - 12663
  • A.M.J.J. Bonvin, S.J. de Vries(2008): How proteins get in touch: Interface prediction in the study of biomolecular complexes. Curr. Pept. and Prot. Research pp. 394 - 406
  • A.M.J.J. Bonvin, M. van Dijk(2008): A protein-DNA docking benchmark. Nucl. Acids Res.
  • B. Berkhout, M Liscaljet, A Land, M Dankers, S.T. Hsu, E. van Anken, A.M.J.J. Bonvin, RW Sander, I Braakman, I Bontjers(2008): Evolution Rescues Folding of HIV-1 Envelope Glycoprotein GP120 Lacking a Conserved Disulfide Bond Mol. Biol. Cell pp. 4707 - 4716
  • A.M.J.J. Bonvin, M. Krzeminski, R. Boelens, G Fuentes(2009): MINOES: a new approach to select a representative ensemble of structures in NMR studies of (partially) unfolded states. Application to d25-PYP. Proteins pp. 894 - 905
  • P.P.C.W. Kemmeren, A.M.J.J. Bonvin, A. Huang, S.J. de Vries, H.Th.M. Timmers, S.J.L. van Wijk, R. Boelens(2009): A comprehensive framework of E2-RING E3 interactions of the human ubiquitin-proteasome system. Mol. Sys. Biol. pp. 295
  • A.M.J.J. Bonvin, M. van Dijk(2009): 3D-DART: a DNA structure modelling server. Nucl. Adic Res. pp. W235 - W239
  • P Gros, JPBA Mannie, CM Reynolds, M.R. Egmond, J Tommssen, C. Raetz, MS Trent, L. Rutten, CM Stead, A.M.J.J. Bonvin(2009): Active site architecture and catalytic mechanism of the lipid A deacylase LpxR of Salmonella typhimurium. Proc. Natl. Acad. Sci. pp. 1960 - 1964
  • M Lu, RW Sanders, D Eggink, JPM Langedijk, AMJJ Bonvin, B Berkhout, Y Deng(2009): Detailed mechanistic insights into HIV-1 sensitivity to three generations fusion inhibitors. J. Biol. Chem. pp. 26941 - 26950
  • Y Deng, R.W. Sanders, D Ekking, J.P.M. Langedijk, A.M.J.J. Bonvin, M Lu, B. Berkhout(2009): Detailed mechanistic insights into HIV-1 sensitivity to three generations fusion inhibitors. J. Biol. Chem. pp. 26941 - 26950
  • G Fuentes, A.M.J.J. Bonvin, A. Perrakis, K. Repanas, S.X. Cohen(2009): Insights into the DNA cleavage mechanism of human LINE-1 retrotransposon endonuclease Proteins pp. 917 - 928
  • T Stockner, A.M.J.J. Bonvin, P Chiba, GF Ecker, S.J. de Vries(2009): Data-driven homology modelling of P-glycoprotein in the ATP-bound state indicates flexibility of the transmembrane domains FEBS Journal pp. 964 - 972
  • R Augustin, M. Hammer, F Anton-Erxleben, A.M.J.J. Bonvin, T. Gutsmann, M Leippe, M Stanisak, J Groetzinger, R Podschun, G Gelhaus, AJ Dingley, TCG Bosch, S.J.A. Jung(2009): Hydramacin-1: Structure and antibacterial activity of a protein from the basal metazoan Hydra J Biol Chem pp. 1896 - 1905
  • M Nilges, A Giachetti, A Cavalli, G.W. Vuister, P Guentert, G van der Schot, D Baker, S Raman, JF Doreleijers, A Bagaria, HRA Jonker, B Mao, TE Malliavin, WF Vranken, B Bardiaux, A Rosato, GT Montelione, A.M.J.J. Bonvin, T.A. Herrmann, P Guerry, YJ Huang(2009): CASD-NMR: Critical Assessment of Automated Structure Determination by NMR. Nature Methods pp. 625 - 626
  • B Ravn, AK Nielsen, R Wimmer, V Sass, S Neve, T Schneider, U Pag, R Wiedemann, PH Mygind, L De Maria, A Jansen, Th Kruse, AMJJ Bonvin, H-H Kristensen, L Kamenova, DS Raventos, H-G Sahl(2010): Plectasin, a fungal defensin antibiotic peptide, targets the bacterial cell wall precursor Lipid II. Science pp. 1168 - 1172
  • AMJJ Bonvin, E AB, G Siegal, M Kobayashi(2010): Structure of the DNA bound BRCT region from human Replication Factor C p140 and model of the protein-DNA complex. J. Biol. Chem. pp. 10087 - 10097
  • G Nicastro, SV Todi, AMJJ Bonvin, E Karaca, A Pastore, HL Paulson(2010): Understanding the Role of the Josephin Domain in the PolyUb Binding and Cleavage Properties of Ataxin-3 PloSONE pp. 1 - 10
  • M Lensch, S Andre, HJ Gabius, AMJJ Bonvin, T Singh, AM Wu, M Krzeminski(2010): Human galectin-3 (Mac-2 antigen): Defining molecular switches of affinity to natural glycoproteins, structural and dynamic aspects of glycan binding by flexible ligand docking and putative regulatory sequences in the proximal promoter region Biochimica et Biophysica Acta pp. 150 - 161
  • A Bordogna, AMJJ Bonvin, PL Kastritis, ASJ Melquiond, M van Dijk, SJ de Vries, JPGLM Rodrigues, E Karaca(2010): Strengths and weaknesses of data-driven docking in CAPRI. Proteins: Structure, Function and Bioinformatics pp. 3242 - 3249
  • M van Dijk, AMJJ Bonvin, SJ de Vries(2010): The HADDOCK web server for data-driven biomolecular docking. Nature Protocols pp. 883 - 897
  • AMJJ Bonvin, PL Kastritis(2010): Are Scoring Functions in Protein-Protein Docking Ready To Predict Interactomes? Clues from a Novel Binding Affinity Benchmark Journal of Proteome Research pp. 2216 - 2225
  • ASJ Melquiond, E Karaca, SJ de Vries, AMJJ Bonvin, PL Kastritis(2010): Building Macromolecular Assemblies by Information-driven Docking Molecular & Cellular Proteomics pp. 1784 - 1794
  • AMJJ Bonvin, M van Dijk(2010): Pushing the limits of what is achievable in protein-DNA docking: benchmarking HADDOCK's performance. Nucleic Acid Research pp. 5634 - 5647
  • R Loth, R Boelens, AMJJ Bonvin, M Krzeminski(2010): SAMPLEX: Automatic mapping of perturbed and unperturbed regions of proteins and complexes. BMC Bioinformatics pp. 51
  • PL Kastritis, YC Fiamegos, A.M.J.J. Bonvin, K Lewis, V Exarchou, MR Hamblin, J Vervoort, GP Tegos, H Han(2011): Antimicrobial and efflux pump inhibitory activity of caffeoylquinic acids from Artemisia absinthium against Gram-positive pathogenic bacteria. PlosONE pp. 1 - 12
  • T Singh, M Lensch, A.M.J.J. Bonvin, AM Wu, H-J Gabius, S Andre, M Krzeminski(2011): Human galectin-3 (Mac-2 antigen): defining molecular switches of affinity to natural glycoproteins, structural and dynamic aspects of glycan binding by flexible ligand docking and putative regulatory sequences in the proximal promoter region. Biochimica et Biophysica Acta pp. 150 - 161
  • A.M.J.J. Bonvin, R Boelens, D Stratman(2011): Quantitative use of chemical shifts for the modelling of protein complexes. Proteins: Struc. Funct. & Bioinformatic pp. 2662 - 2670
  • A.M.J.J. Bonvin, M Okon, E Escobar-Cabrera, DKW Lau, CF Dart, LP McIntosh(2011): Characterizing the N- and C-terminal SUMO interacting motifs of the scaffold protein DAXX. J Biol Chem pp. 19816 - 19829
  • A.M.J.J. Bonvin, SJ de Vries(2011): CPORT: a Consensus Interface Predictor and its Performance in Prediction-driven Docking with HADDOCK. PlosONE pp. 1 - 12
  • A.M.J.J. Bonvin, C Schmitz(2011): Protein-Protein HADDocking using exclusively Pseudocontact Shifts. J Biomol NMR pp. 263 - 266
  • A.M.J.J. Bonvin, E Karaca(2011): A multi-domain flexible docking approach to deal with large conformational changes in the modeling of biomolecular complexes. Structure pp. 555 - 565
  • Z Weng, H Hwang, IH Moal, PA Bates, J Janin, P Kastritis, A.M.J.J. Bonvin(2011): A structure-based benchmark for protein-protein binding affinity. Protein Science pp. 482 - 491
  • M. Weingarth, C. Ader, A.S.J. Melquiond, D. Nand, O. Pongs, S. Becker, A.M.J.J. Bonvin, M. Baldus(2012): Supramolecular structure of membrane-associated polypeptides by combining solid-state NMR and Molecular Dynamics simulations. Biophys. J. pp. 29 - 37
  • S.J.L. de Vries, A.S.J. Melquiond, S.J. de Vries, H.Th.M. Timmers, A.M.J.J. Bonvin(2012): Dynamic control of selectivity in E2-E3 interactions via a salt-bridge network revealed by an ASP to GLU substitution. PLoS Comp. Biol. pp. 1 - 9
  • A.S.J. Melquiond, E. Karaca, P.L. Kastritis, A.M.J.J. Bonvin(2012): Next challenges in protein-protein docking: From proteome to interactome and beyond. WIREs Computational Molecular Science pp. 642 - 651
  • J.P.G.L.M. Rodrigues, M. Trellet, C. Schmitz, P.L. Kastritis, E. Karaca, A.S.J. Melquiond, A.M.J.J. Bonvin(2012): Clustering biomolecular complexes by residue contacts similarity. Proteins: Struc. Funct. & Bioinformatics pp. 1810 - 1870
  • P.L. Kastritis, K.M. Visscher, A.D.J. van Dijk, A.M.J.J. Bonvin(2013): Solvated docking using Kyte-Doolittle-based water propensities Proteins: Struct. Funct. & Bioinformatics pp. 510 - 518
  • M. Weingarth, A. Prokofyev, E. van der Cruijsen, D. Nand, A.M.J.J. Bonvin, M. Baldus(2013): Structural determinants and functional aspects of specific lipid binding to potassium channels. J. Am. Chem. Soc. pp. 3983 - 3988
  • P.L. Kastritis, A.M.J.J. Bonvin(2013): On the binding affinity of macromolecular interactions: daring to ask why proteins interact J. R. Soc. Interface pp. 1 - 27
  • (2013): Molecular origins of binding affinity: seeking the Archimedean point Current Opinion in Structural Biology pp. 868 - 877
  • E. Karaca, A.M.J.J. Bonvin(2013): Advances in integrated modelling of biomolecular complexes Methods pp. 372 - 381
  • M. van Dijk, K. Visscher, P.L. Kastritis, A.M.J.J. Bonvin(2013): Solvated protein-DNA docking using HADDOCK. J. Biomol. NMR pp. 51 - 63
  • D.L. Hulsig, Y.Y. Liu, N.M. Strokappe, S. Battella, M. El Khattabi, L.E. Mc Coy, A. Hinz, M. Hock, A.M.J.J. Bonvin, J.P.M. Langedijk, D. Davis, A. Forsman Quinley, M. Aasa-Chapman, R.A. Weiss, C.T. Verrips, W. Weissenhorn, L. Rutten(2013): A gp41 MPER-specific Llama VHH Requires a Hydrophobic CDR3 for Neutralization but not for Antigen Recognition. PLoS Pathogens pp. e1003203 - 16
  • P.L. Kastritis, A.M.J.J. Bonvin(2013): Molecular origins of binding affinity: Seeking the Archimedean point. Current Opinion in Structural Biology pp. 868 - 877
  • M. Weingarth, C. Ader, A.S.J. Melquiond, D. Nand, O Pongs, S. Becker, A.M.J.J. Bonvin, M. Baldus(2013): Supramolecular structure of membrane-associated polypeptides by combining solid-state NMR and Molecular Dynamics simulations. Biophysical Journal pp. 29 - 37
  • A.M.J.J. Bonvin, M. Pazgier, K.M. Varney, J. Malin, W. Yu, E. Ateh, T. Oashi, J. Huang, W. Lu, M. Diepeveen-de Bruin, J. Bryant, E. Breukink, A.D. MacKerell Jr., E.P.H. de Leeuw(2013): Turning Defense into Offense: Development of Defensin Mimetics as Novel Antibiotics targeting Lipid II. PLoS Pathogens pp. e1003732 - 14
  • S. Alex, K. Lange, T. Amolo, J.S. Grinstead, E. Szalowska, A. Koppen, K. Mudde, D. Haenen, S. Al-Lahham, H. Roelofsen, R. Houtman, B. van der Burg, A.M.J.J. Bonvin, E. Kalkhoven, M. Muller, G. Hooiveld, S. Kersten(2013): Short chain fatty acids stimulate Angptl4 synthesis in human colonocytes by selective PPAR modulation. Mol. Cell. Biol. pp. 1303 - 1316
  • E. Karaca, A.M.J.J. Bonvin(2013): On the usefulness of Ion Mobility Mass Spectrometry and SAXS data in scoring docking decoys. Acta Cryst D pp. 683 - 694
  • D.M. Dias, J.P.G.L.M. Rodrigues, N.S. Domingues, A.M.J.J. Bonvin, M.C.A. Castro(2013): Unveiling the Interaction of Vanadium Compounds with Human Serum Albumin using 1H STD NMR and Computational Docking Studies Eur. J. Inorg. Chem pp. 4619 - 4626
  • M. Trellet, A.S.J. Melquiond, A.M.J.J. Bonvin(2013): A Unified Conformational Selection and Induced Fit Approach to Protein-Peptide Docking. PLoS ONE pp. e58769 - 13
  • J. Hennig, S. de Vries, K.D.M. Hennig, L. Randles, K.J. Walters, M. Sunnerhagen, A.M.J.J. Bonvin(2013): MTMDAT-HADDOCK: High-throughput, protein complex structure modeling based on limited proteolysis and mass spectrometry BMC Struct. Biol. pp. 1 - 11
  • J.P.G.L.M. Rodrigues, A.S.J. Melquiond, E. Karaca, M. Trellet, M. van Dijk, G.C.P. van Zundert, C. Schmitz, S.J. de Vries, A. Bordogna, L. Bonati, P.L. Kastritis, A.M.J.J. Bonvin(2013): Defining the limits of homology modelling in information-driven protein docking Proteins: Struct. Funct. & Bioinformatics pp. 2119 - 2128
  • E.A.W. van der Cruijsen, D. Nand, M. Weingarth, A. Prokofyev, S. Hornig, A.M.J.J. Bonvin, S. Becker, R.E. Hulse, E. Perozo, O. Pongs, M. Baldus(2013): The importance of the lipid-pore loop interface for potassium channel structure and function. Proc. Natl. Acad. Sci. USA pp. 13008 - 13013
  • J. Snijder, R.J. Burnley, A. Wiegard, A.S.J. Melquiond, A.M.J.J. Bonvin, I.M. Axmann, A.J.R. Heck(2014): Insight into cyanobacterial circadian timing from structural details of the KaiB?KaiC interaction Proc. Natl. Acad. Sci. USA pp. 1379 - 1383
  • P.L. Kastritis, J.P.G.L.M. Rodrigues, A.M.J.J. Bonvin(2014): HADDOCK2P2I: A robust biophysical model for predicting the binding affinity of protein-protein interaction inhibitors J. Chem. Inf. Mod. pp. 826 - 836

Professionele publicatie

  • M van Dijk, A.M.J.J. Bonvin, S.J. de Vries(2009): The HADDOCK web server
  • M. van Dijk, A.M.J.J. Bonvin(2009): The 3D-DART DNA modelling web server


  • J. Janin, A.M.J.J. Bonvin(2013): Protein-Protein Interactions.
  • A.M.J.J. Bonvin(2013): Coming to peace with protein complexes? 5th CAPRI evaluation meeting, April 17-19th 2013, Utrecht.
  • A.M.J.J. Bonvin(2013): Alexandre Bonvin (Universiteit Utrecht): ?We brengen het sociale leven van een molecuul in kaart
  • (2013): "Ik wil de fundamenten van het leven begrijpen"





Prof. dr. A.M.J.J. Bonvin

Verbonden aan

University of Puget Sound, Anthropology, Comparative Sociology


Prof. dr. A.M.J.J. Bonvin, Dr. E. Karaca, Dr. P.L. Kastritis, Dr. A. Melquiond, Dr. C.P.F. Schmitz, Dr. S.J. de Vries


01/09/2007 tot 14/07/2014