A survey of available tools and web servers for analysis of protein-protein interactions and interfaces

The unanimous agreement that cellular processes are (largely) governed by interactions between proteins has led to enormous community efforts culminating in overwhelming information relating to these proteins; to the regulation of their interactions, to the way in which they interact and to the function which is determined by these interactions. These data have been organized in databases and servers. However, to make these really useful, it is essential not only to be aware of these, but in particular to have a working knowledge of which tools to use for a given problem; what are the tool advantages and drawbacks; and no less important how to combine these for a particular goal since usually it is not one tool, but some combination of tool-modules that is needed. This is the goal of this review.

[1]  Ruth Nussinov,et al.  Geometry‐based flexible and symmetric protein docking , 2005, Proteins.

[2]  R. Raz,et al.  ProMate: a structure based prediction program to identify the location of protein-protein binding sites. , 2004, Journal of molecular biology.

[3]  Thomas Lengauer,et al.  Alignment of Non-Covalent Interactions at Protein-Protein Interfaces , 2008, PloS one.

[4]  David R. Westhead,et al.  Improved prediction of protein-protein binding sites using a support vector machines approach. , 2005, Bioinformatics.

[5]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[6]  Kurt S. Thorn,et al.  ASEdb: a database of alanine mutations and their effects on the free energy of binding in protein interactions , 2001, Bioinform..

[7]  Narayanaswamy Srinivasan,et al.  Nucleic Acids Research Advance Access published June 21, 2007 PIC: Protein Interactions Calculator , 2007 .

[8]  Michael Schroeder,et al.  SCOPPI: a structural classification of protein–protein interfaces , 2005, Nucleic Acids Res..

[9]  Katja M. Arndt,et al.  An in vivo library-versus-library selection of optimized protein–protein interactions , 1999, Nature Biotechnology.

[10]  Benjamin A. Shoemaker,et al.  Finding biologically relevant protein domain interactions: Conserved binding mode analysis , 2006, Protein science : a publication of the Protein Society.

[11]  Gary D Bader,et al.  Systematic Genetic Analysis with Ordered Arrays of Yeast Deletion Mutants , 2001, Science.

[12]  Kengo Kinoshita,et al.  PreBI: prediction of biological interfaces of proteins in crystals , 2006, Nucleic Acids Res..

[13]  M. Schroeder,et al.  Using protein binding site prediction to improve protein docking. , 2008, Gene.

[14]  R. Norel,et al.  Electrostatic aspects of protein-protein interactions. , 2000, Current opinion in structural biology.

[15]  N. Ben-Tal,et al.  The ConSurf‐HSSP database: The mapping of evolutionary conservation among homologs onto PDB structures , 2004, Proteins.

[16]  C. Dominguez,et al.  HADDOCK: a protein-protein docking approach based on biochemical or biophysical information. , 2003, Journal of the American Chemical Society.

[17]  Sergey Lyskov,et al.  The RosettaDock server for local protein–protein docking , 2008, Nucleic Acids Res..

[18]  S. Sakiyama,et al.  Loss of Raf-1-binding activity of v-Ha-Ras by the deletion of amino acid residues 64-72 and 143-151. , 1996, Cellular signalling.

[19]  C. Chothia,et al.  The atomic structure of protein-protein recognition sites. , 1999, Journal of molecular biology.

[20]  A J Olson,et al.  Morphology of protein-protein interfaces. , 1998, Structure.

[21]  J. Thornton,et al.  PQS: a protein quaternary structure file server. , 1998, Trends in biochemical sciences.

[22]  Pinak Chakrabarti,et al.  Hydration of protein–protein interfaces , 2005, Proteins.

[23]  Igor Jurisica,et al.  Online Predicted Human Interaction Database , 2005, Bioinform..

[24]  S. Jones,et al.  Analysis of protein-protein interaction sites using surface patches. , 1997, Journal of molecular biology.

[25]  James R. Knight,et al.  A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae , 2000, Nature.

[26]  D. Ritchie,et al.  Protein docking using spherical polar Fourier correlations , 2000, Proteins.

[27]  Tal Pupko,et al.  Structural Genomics , 2005 .

[28]  Sarah A. Teichmann,et al.  Principles of protein-protein interactions , 2002, ECCB.

[29]  International Human Genome Sequencing Consortium.  Initial sequencing and analysis of the human genome , 2001, Nature.

[30]  Burkhard Rost,et al.  Protein–Protein Interaction Hotspots Carved into Sequences , 2007, PLoS Comput. Biol..

[31]  D. Baker,et al.  A simple physical model for binding energy hot spots in protein–protein complexes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[32]  R. Nussinov,et al.  Protein binding versus protein folding: the role of hydrophilic bridges in protein associations. , 1997, Journal of molecular biology.

[33]  R. Nussinov,et al.  Conservation of polar residues as hot spots at protein interfaces , 2000, Proteins.

[34]  L. Serrano,et al.  Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations. , 2002, Journal of molecular biology.

[35]  R. M. Burnett,et al.  Distribution and complementarity of hydropathy in mutisunit proteins , 1991, Proteins.

[36]  Daniel R. Caffrey,et al.  Are protein–protein interfaces more conserved in sequence than the rest of the protein surface? , 2004, Protein science : a publication of the Protein Society.

[37]  Burkhard Rost,et al.  ISIS: interaction sites identified from sequence , 2007, Bioinform..

[38]  D. Bailey,et al.  The Binding Interface Database (BID): A Compilation of Amino Acid Hot Spots in Protein Interfaces , 2003, Bioinform..

[39]  Deok-Soo Kim,et al.  A protein domain interaction interface database: InterPare , 2005, BMC Bioinformatics.

[40]  Teresa M. Przytycka,et al.  DOMINE: a database of protein domain interactions , 2007, Nucleic Acids Res..

[41]  Fred P. Davis,et al.  PIBASE: a comprehensive database of structurally defined protein interfaces , 2005, Bioinform..

[42]  Olivier Lichtarge,et al.  BIOINFORMATICS ORIGINAL PAPER Systems biology , 2004 .

[43]  Ozlem Keskin,et al.  HotSprint: database of computational hot spots in protein interfaces , 2007, Nucleic Acids Res..

[44]  C. Chothia,et al.  The structure of protein-protein recognition sites. , 1990, The Journal of biological chemistry.

[45]  Ioannis Xenarios,et al.  DIP, the Database of Interacting Proteins: a research tool for studying cellular networks of protein interactions , 2002, Nucleic Acids Res..

[46]  K. Henrick,et al.  Inference of macromolecular assemblies from crystalline state. , 2007, Journal of molecular biology.

[47]  Akinori Sarai,et al.  ProTherm and ProNIT: thermodynamic databases for proteins and protein–nucleic acid interactions , 2005, Nucleic Acids Res..

[48]  Ozlem Keskin,et al.  Architectures and functional coverage of protein-protein interfaces. , 2008, Journal of molecular biology.

[49]  Luhua Lai,et al.  Structure-based method for analyzing protein–protein interfaces , 2004, Journal of molecular modeling.

[50]  Tammy M. K. Cheng,et al.  pyDock: Electrostatics and desolvation for effective scoring of rigid‐body protein–protein docking , 2007, Proteins.

[51]  J. Thornton,et al.  Protein–protein interfaces: Analysis of amino acid conservation in homodimers , 2001, Proteins.

[52]  Hongbo Zhu,et al.  NOXclass: prediction of protein-protein interaction types , 2006, BMC Bioinformatics.

[53]  Holger Gohlke,et al.  Targeting protein-protein interactions with small molecules: challenges and perspectives for computational binding epitope detection and ligand finding. , 2006, Current medicinal chemistry.

[54]  S. Vajda,et al.  Anchor residues in protein-protein interactions. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[55]  J M Thornton,et al.  LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. , 1995, Protein engineering.

[56]  J M Thornton,et al.  Conservation helps to identify biologically relevant crystal contacts. , 2001, Journal of molecular biology.

[57]  Richard M. Jackson,et al.  Q-SiteFinder: an energy-based method for the prediction of protein-ligand binding sites , 2005, Bioinform..

[58]  Byungkyu Brian Park,et al.  HPID: The Human Protein Interaction Database , 2004, Bioinform..

[59]  A. Giuliani,et al.  A computational approach identifies two regions of Hepatitis C Virus E1 protein as interacting domains involved in viral fusion process , 2009, BMC Structural Biology.

[60]  S. Jones,et al.  Protein domain interfaces: characterization and comparison with oligomeric protein interfaces. , 2000, Protein engineering.

[61]  P. Argos.  An investigation of protein subunit and domain interfaces. , 1988, Protein engineering.

[62]  Kyungsook Han,et al.  PSIbase: a database of Protein Structural Interactome map (PSIMAP) , 2005, Bioinform..

[63]  Julie C. Mitchell,et al.  KFC Server: interactive forecasting of protein interaction hot spots , 2008, Nucleic Acids Res..

[64]  Ozlem Keskin,et al.  Prediction of protein-protein interactions by combining structure and sequence conservation in protein interfaces , 2005, Bioinform..

[65]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[66]  Julie Bernauer,et al.  DiMoVo: a Voronoi tessellation-based method for discriminating crystallographic and biological protein-protein interactions , 2008, Bioinform..

[67]  G. P. Smith,et al.  Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. , 1985, Science.

[68]  R. Nussinov,et al.  Protein–protein interactions: Structurally conserved residues distinguish between binding sites and exposed protein surfaces , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[69]  Itay Mayrose,et al.  Rate4Site: an algorithmic tool for the identification of functional regions in proteins by surface mapping of evolutionary determinants within their homologues , 2002, ISMB.

[70]  P Argos,et al.  Hydrophobic patches on the surfaces of protein structures , 1996, Proteins.

[71]  Zhiping Weng,et al.  Docking unbound proteins using shape complementarity, desolvation, and electrostatics , 2002, Proteins.

[72]  C. Camacho,et al.  Modeling side‐chains using molecular dynamics improve recognition of binding region in CAPRI targets , 2005, Proteins.

[73]  Francis Rodier,et al.  Protein–protein interaction at crystal contacts , 1995, Proteins.

[74]  Alfonso Valencia,et al.  firestar—prediction of functionally important residues using structural templates and alignment reliability , 2007, Nucleic Acids Res..

[75]  I R Vetter,et al.  Dynamic properties of the Ras switch I region and its importance for binding to effectors , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[76]  L. T. Ten Eyck,et al.  Protein docking using continuum electrostatics and geometric fit. , 2001, Protein engineering.

[77]  H. Wolfson,et al.  Recognition of Functional Sites in Protein Structures☆ , 2004, Journal of Molecular Biology.

[78]  R. Powers,et al.  Comparison of protein active site structures for functional annotation of proteins and drug design , 2006, Proteins.

[79]  Harianto Tjong,et al.  DISPLAR: an accurate method for predicting DNA-binding sites on protein surfaces , 2007, Nucleic acids research.

[80]  J. Janin,et al.  Dissecting protein–protein recognition sites , 2002, Proteins.

[81]  Roman A. Laskowski,et al.  PDBsum: summaries and analyses of PDB structures , 2001, Nucleic Acids Res..

[82]  Zhiping Weng,et al.  A protein–protein docking benchmark , 2003, Proteins.

[83]  Emil Alexov,et al.  Nucleic Acids Research Advance Access published October 28, 2006 PROTCOM: searchable database of protein complexes enhanced with domain–domain structures , 2006 .

[84]  Huan‐Xiang Zhou,et al.  Prediction of solvent accessibility and sites of deleterious mutations from protein sequence , 2005, Nucleic acids research.

[85]  R. Laskowski.  SURFNET: a program for visualizing molecular surfaces, cavities, and intermolecular interactions. , 1995, Journal of molecular graphics.

[86]  Ruth Nussinov,et al.  Structural motifs at protein‐protein interfaces: Protein cores versus two‐state and three‐state model complexes , 1997, Protein science : a publication of the Protein Society.

[87]  Miriam Eisenstein,et al.  Electrostatics in protein–protein docking , 2002, Protein science : a publication of the Protein Society.

[88]  Michael Schroeder,et al.  SCOWLP: a web-based database for detailed characterization and visualization of protein interfaces , 2006, BMC Bioinformatics.

[89]  B. Rost,et al.  Analysing six types of protein-protein interfaces. , 2003, Journal of molecular biology.

[90]  Oliviero Carugo,et al.  Protein—protein crystal‐packing contacts , 1997, Protein science : a publication of the Protein Society.

[91]  M. Teresa Pisabarro,et al.  SCOWLP classification: Structural comparison and analysis of protein binding regions , 2008, BMC Bioinformatics.

[92]  D. F. Waugh,et al.  Protein-protein interactions. , 1954, Advances in protein chemistry.

[93]  Jie Liang,et al.  Protein-protein interactions: hot spots and structurally conserved residues often locate in complemented pockets that pre-organized in the unbound states: implications for docking. , 2004, Journal of molecular biology.

[94]  F. Regnier,et al.  Protein-protein interactions on weak-cation-exchange sorbent surfaces during chromatographic separations. , 1998, Journal of chromatography. A.

[95]  Song Liu,et al.  Protein binding site prediction using an empirical scoring function , 2006, Nucleic acids research.

[96]  J Kuriyan,et al.  Structure-based Mutagenesis Reveals Distinct Functions for Ras Switch 1 and Switch 2 in Sos-catalyzed Guanine Nucleotide Exchange* , 2001, The Journal of Biological Chemistry.

[97]  K Schulten,et al.  VMD: visual molecular dynamics. , 1996, Journal of molecular graphics.

[98]  H. Wolfson,et al.  Shape complementarity at protein–protein interfaces , 1994, Biopolymers.

[99]  François Stricher,et al.  The FoldX web server: an online force field , 2005, Nucleic Acids Res..

[100]  M. Sternberg,et al.  Modelling protein docking using shape complementarity, electrostatics and biochemical information. , 1997, Journal of molecular biology.

[101]  C. Landry,et al.  An in Vivo Map of the Yeast Protein Interactome , 2008, Science.

[102]  Janet M. Thornton,et al.  Automatic inference of protein quaternary structure from crystals , 2003 .

[103]  G. Marriott,et al.  Analysis of protein interactions using fluorescence technologies. , 2003, Current opinion in chemical biology.

[104]  R. Nussinov,et al.  Protein–protein interactions: organization, cooperativity and mapping in a bottom-up Systems Biology approach , 2005, Physical biology.

[105]  M. Sternberg,et al.  Rapid refinement of protein interfaces incorporating solvation: application to the docking problem. , 1998, Journal of molecular biology.

[106]  R Nussinov,et al.  Hydrophobic folding units at protein‐protein interfaces: Implications to protein folding and to protein‐protein association , 1997, Protein science : a publication of the Protein Society.

[107]  Pedro A Fernandes,et al.  Hot spot occlusion from bulk water: a comprehensive study of the complex between the lysozyme HEL and the antibody FVD1.3. , 2007, The journal of physical chemistry. B.

[108]  G. Wiederschain.  Protein-protein interactions. A molecular cloning manual , 2006, Biochemistry (Moscow).

[109]  Ian M. Donaldson,et al.  BIND: the Biomolecular Interaction Network Database , 2001, Nucleic Acids Res..

[110]  Dipanwita Roy Chowdhury,et al.  Human protein reference database as a discovery resource for proteomics , 2004, Nucleic Acids Res..

[111]  W. Delano.  Unraveling hot spots in binding interfaces: progress and challenges. , 2002, Current opinion in structural biology.

[112]  Aleksey A. Porollo,et al.  Prediction‐based fingerprints of protein–protein interactions , 2006, Proteins.

[113]  Dmitrij Frishman,et al.  MIPS: a database for genomes and protein sequences , 1999, Nucleic Acids Res..

[114]  S. Schreiber,et al.  Printing proteins as microarrays for high-throughput function determination. , 2000, Science.

[115]  H. Wolfson,et al.  A dataset of protein-protein interfaces generated with a sequence-order-independent comparison technique. , 1996, Journal of molecular biology.

[116]  Sandor Vajda,et al.  ClusPro: a fully automated algorithm for protein-protein docking , 2004, Nucleic Acids Res..

[117]  Andrey Tovchigrechko,et al.  GRAMM-X public web server for protein–protein docking , 2006, Nucleic Acids Res..

[118]  Robin F. B. Turner,et al.  Increasing the efficiency of SAGE adaptor ligation by directed ligation chemistry. , 2004, Nucleic acids research.

[119]  Huan‐Xiang Zhou,et al.  Prediction of protein interaction sites from sequence profile and residue neighbor list , 2001, Proteins.

[120]  Benjamin A. Shoemaker,et al.  Deciphering Protein–Protein Interactions. Part I. Experimental Techniques and Databases , 2007, PLoS Comput. Biol..

[121]  Susan Jones,et al.  SHARP2: protein-protein interaction predictions using patch analysis , 2006, Bioinform..

[122]  R C Wade,et al.  MolSurfer: two-dimensional maps for navigating three-dimensional structures of proteins. , 1999, Trends in biochemical sciences.

[123]  Gabriele Ausiello,et al.  MINT: the Molecular INTeraction database , 2006, Nucleic Acids Res..

[124]  David E. Kim,et al.  Computational Alanine Scanning of Protein-Protein Interfaces , 2004, Science's STKE.

[125]  A. Giuliani,et al.  ProFace: a server for the analysis of the physicochemical features of protein-protein interfaces , 2006 .

[126]  Yael Mandel-Gutfreund,et al.  Annotating nucleic acid-binding function based on protein structure. , 2003, Journal of molecular biology.

[127]  R. Nussinov,et al.  Hot regions in protein--protein interactions: the organization and contribution of structurally conserved hot spot residues. , 2005, Journal of molecular biology.

[128]  Janet M. Thornton,et al.  ProFunc: a server for predicting protein function from 3D structure , 2005, Nucleic Acids Res..

[129]  Ruth Nussinov,et al.  PatchDock and SymmDock: servers for rigid and symmetric docking , 2005, Nucleic Acids Res..

[130]  R. Nussinov,et al.  Favorable scaffolds: proteins with different sequence, structure and function may associate in similar ways. , 2005, Protein engineering, design & selection : PEDS.

[131]  Barry Honig,et al.  On the role of electrostatic interactions in the design of protein-protein interfaces. , 2002, Journal of molecular biology.

[132]  Harianto Tjong,et al.  PI2PE: protein interface/interior prediction engine , 2007, Nucleic Acids Res..

[133]  R. Ozawa,et al.  A comprehensive two-hybrid analysis to explore the yeast protein interactome , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[134]  Werner Braun,et al.  InterProSurf: a web server for predicting interacting sites on protein surfaces , 2007, Bioinform..

[135]  Jie Liang,et al.  CASTp: computed atlas of surface topography of proteins with structural and topographical mapping of functionally annotated residues , 2006, Nucleic Acids Res..

[136]  A. Bogan,et al.  Anatomy of hot spots in protein interfaces. , 1998, Journal of molecular biology.

[137]  Ruth Nussinov,et al.  FireDock: Fast interaction refinement in molecular docking , 2007, Proteins.

[138]  H. Wolfson,et al.  Studies of protein‐protein interfaces: A statistical analysis of the hydrophobic effect , 1997, Protein science : a publication of the Protein Society.

[139]  R. Karlsson,et al.  SPR for molecular interaction analysis: a review of emerging application areas , 2004, Journal of molecular recognition : JMR.

[140]  Peter A. Kollman,et al.  Computational alanine scanning of the 1:1 human growth hormone–receptor complex , 2002, J. Comput. Chem..

[141]  Christian von Mering,et al.  STRING 7—recent developments in the integration and prediction of protein interactions , 2006, Nucleic Acids Res..

[142]  Ozlem Keskin,et al.  Characterization and prediction of protein interfaces to infer protein-protein interaction networks. , 2008, Current pharmaceutical biotechnology.

[143]  Joan Teyra,et al.  Characterization of interfacial solvent in protein complexes and contribution of wet spots to the interface description , 2007, Proteins.

[144]  Joël Janin,et al.  Specific versus non-specific contacts in protein crystals , 1997, Nature Structural Biology.

[145]  Huan-Xiang Zhou,et al.  Interaction-site prediction for protein complexes: a critical assessment , 2007, Bioinform..

[146]  W. S. Valdar,et al.  Scoring residue conservation , 2002, Proteins.

[147]  Ozlem Keskin,et al.  PRISM: protein interactions by structural matching , 2005, Nucleic Acids Res..

[148]  B. Séraphin,et al.  A generic protein purification method for protein complex characterization and proteome exploration , 1999, Nature Biotechnology.

[149]  Andrew J. Bordner,et al.  Comprehensive inventory of protein complexes in the Protein Data Bank from consistent classification of interfaces , 2008, BMC Bioinformatics.

[150]  Jinn-Moon Yang,et al.  3D-partner: a web server to infer interacting partners and binding models , 2007, Nucleic Acids Res..

[151]  Mike Tyers,et al.  BioGRID: a general repository for interaction datasets , 2005, Nucleic Acids Res..

[152]  Ruth Nussinov,et al.  MultiBind and MAPPIS: webservers for multiple alignment of protein 3D-binding sites and their interactions , 2008, Nucleic Acids Res..

[153]  Robert B. Russell,et al.  3did: interacting protein domains of known three-dimensional structure , 2004, Nucleic Acids Res..

[154]  J. Janin,et al.  Dissecting subunit interfaces in homodimeric proteins , 2003, Proteins.

[155]  Alejandro Panjkovich,et al.  3did Update: domain–domain and peptide-mediated interactions of known 3D structure , 2008, Nucleic Acids Res..

[156]  T. Clackson,et al.  A hot spot of binding energy in a hormone-receptor interface , 1995, Science.

[157]  C. Chothia,et al.  Principles of protein–protein recognition , 1975, Nature.

[158]  Martin Vingron,et al.  IntAct: an open source molecular interaction database , 2004, Nucleic Acids Res..

[159]  Jie Liang,et al.  Estimation of amino acid residue substitution rates at local spatial regions and application in protein function inference: a Bayesian Monte Carlo approach. , 2006, Molecular biology and evolution.

[160]  H. Wolfson,et al.  A new, structurally nonredundant, diverse data set of protein–protein interfaces and its implications , 2004, Protein science : a publication of the Protein Society.