1xxm Citations

The modular architecture of protein-protein binding interfaces.

Proc Natl Acad Sci U S A 102 57-62 (2005)
Cited: 154 times
EuropePMC logo PMID: 15618400

Abstract

Protein-protein interactions are essential for life. Yet, our understanding of the general principles governing binding is not complete. In the present study, we show that the interface between proteins is built in a modular fashion; each module is comprised of a number of closely interacting residues, with few interactions between the modules. The boundaries between modules are defined by clustering the contact map of the interface. We show that mutations in one module do not affect residues located in a neighboring module. As a result, the structural and energetic consequences of the deletion of entire modules are surprisingly small. To the contrary, within their module, mutations cause complex energetic and structural consequences. Experimentally, this phenomenon is shown on the interaction between TEM1-beta-lactamase and beta-lactamase inhibitor protein (BLIP) by using multiple-mutant analysis and x-ray crystallography. Replacing an entire module of five interface residues with Ala created a large cavity in the interface, with no effect on the detailed structure of the remaining interface. The modular architecture of binding sites, which resembles human engineering design, greatly simplifies the design of new protein interactions and provides a feasible view of how these interactions evolved.

Articles - 1xxm mentioned but not cited (2)

  1. The modular architecture of protein-protein binding interfaces. Reichmann D, Rahat O, Albeck S, Meged R, Dym O, Schreiber G. Proc Natl Acad Sci U S A 102 57-62 (2005)
  2. The structure of BVU2987 from Bacteroides vulgatus reveals a superfamily of bacterial periplasmic proteins with possible inhibitory function. Das D, Finn RD, Carlton D, Miller MD, Abdubek P, Astakhova T, Axelrod HL, Bakolitsa C, Chen C, Chiu HJ, Chiu M, Clayton T, Deller MC, Duan L, Ellrott K, Ernst D, Farr CL, Feuerhelm J, Grant JC, Grzechnik A, Han GW, Jaroszewski L, Jin KK, Klock HE, Knuth MW, Kozbial P, Krishna SS, Kumar A, Marciano D, McMullan D, Morse AT, Nigoghossian E, Nopakun A, Okach L, Puckett C, Reyes R, Rife CL, Sefcovic N, Tien HJ, Trame CB, van den Bedem H, Weekes D, Wooten T, Xu Q, Hodgson KO, Wooley J, Elsliger MA, Deacon AM, Godzik A, Lesley SA, Wilson IA. Acta Crystallogr Sect F Struct Biol Cryst Commun 66 1265-1273 (2010)


Reviews citing this publication (23)

  1. Microscale thermophoresis quantifies biomolecular interactions under previously challenging conditions. Seidel SA, Dijkman PM, Lea WA, van den Bogaart G, Jerabek-Willemsen M, Lazic A, Joseph JS, Srinivasan P, Baaske P, Simeonov A, Katritch I, Melo FA, Ladbury JE, Schreiber G, Watts A, Braun D, Duhr S. Methods 59 301-315 (2013)
  2. Protein-protein interaction and quaternary structure. Janin J, Bahadur RP, Chakrabarti P. Q Rev Biophys 41 133-180 (2008)
  3. Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell. Wei G, Xi W, Nussinov R, Ma B. Chem Rev 116 6516-6551 (2016)
  4. Higher-throughput, label-free, real-time molecular interaction analysis. Rich RL, Myszka DG. Anal Biochem 361 1-6 (2007)
  5. The molecular architecture of protein-protein binding sites. Reichmann D, Rahat O, Cohen M, Neuvirth H, Schreiber G. Curr Opin Struct Biol 17 67-76 (2007)
  6. Features of protein-protein interactions that translate into potent inhibitors: topology, surface area and affinity. Smith MC, Gestwicki JE. Expert Rev Mol Med 14 e16 (2012)
  7. Molecular and cellular approaches for the detection of protein-protein interactions: latest techniques and current limitations. Lalonde S, Ehrhardt DW, Loqué D, Chen J, Rhee SY, Frommer WB. Plant J 53 610-635 (2008)
  8. The importance of being tyrosine: lessons in molecular recognition from minimalist synthetic binding proteins. Koide S, Sidhu SS. ACS Chem Biol 4 325-334 (2009)
  9. Structure and functions of the human amyloid precursor protein: the whole is more than the sum of its parts. Gralle M, Ferreira ST. Prog Neurobiol 82 11-32 (2007)
  10. The design, structures and therapeutic potential of protein epitope mimetics. Robinson JA, Demarco S, Gombert F, Moehle K, Obrecht D. Drug Discov Today 13 944-951 (2008)
  11. Hot spots in protein-protein interfaces: towards drug discovery. Cukuroglu E, Engin HB, Gursoy A, Keskin O. Prog Biophys Mol Biol 116 165-173 (2014)
  12. Computational design of peptide ligands. Vanhee P, van der Sloot AM, Verschueren E, Serrano L, Rousseau F, Schymkowitz J. Trends Biotechnol 29 231-239 (2011)
  13. Survey of the year 2005 commercial optical biosensor literature. Rich RL, Myszka DG. J Mol Recognit 19 478-534 (2006)
  14. The Molecular Origin of Enthalpy/Entropy Compensation in Biomolecular Recognition. Fox JM, Zhao M, Fink MJ, Kang K, Whitesides GM. Annu Rev Biophys 47 223-250 (2018)
  15. The construction of an amino acid network for understanding protein structure and function. Yan W, Zhou J, Sun M, Chen J, Hu G, Shen B. Amino Acids 46 1419-1439 (2014)
  16. An overview of recent advances in structural bioinformatics of protein-protein interactions and a guide to their principles. Sudha G, Nussinov R, Srinivasan N. Prog Biophys Mol Biol 116 141-150 (2014)
  17. Insights into the quaternary association of proteins through structure graphs: a case study of lectins. Brinda KV, Surolia A, Vishveshwara S. Biochem J 391 1-15 (2005)
  18. Targeting protein-protein interactions in hematologic malignancies: still a challenge or a great opportunity for future therapies? Cierpicki T, Grembecka J. Immunol Rev 263 279-301 (2015)
  19. Druggable orthosteric and allosteric hot spots to target protein-protein interactions. Ma B, Nussinov R. Curr Pharm Des 20 1293-1301 (2014)
  20. Max Bergmann lecture protein epitope mimetics in the age of structural vaccinology. Robinson JA. J Pept Sci 19 127-140 (2013)
  21. The oncogenic potential of small nuclear ribonucleoprotein polypeptide G: a comprehensive and perspective view. Mabonga L, Kappo AP. Am J Transl Res 11 6702-6716 (2019)
  22. Small Molecule Agents Targeting PD-1 Checkpoint Pathway for Cancer Immunotherapy: Mechanisms of Action and Other Considerations for Their Advanced Development. Sasikumar PG, Ramachandra M. Front Immunol 13 752065 (2022)
  23. Network Re-Wiring During Allostery and Protein-Protein Interactions: A Graph Spectral Approach. Gadiyaram V, Dighe A, Ghosh S, Vishveshwara S. Methods Mol Biol 2253 89-112 (2021)

Articles citing this publication (129)

  1. Crystal structure of an ancient protein: evolution by conformational epistasis. Ortlund EA, Bridgham JT, Redinbo MR, Thornton JW. Science 317 1544-1548 (2007)
  2. SARS-CoV-2 variant prediction and antiviral drug design are enabled by RBD in vitro evolution. Zahradník J, Marciano S, Shemesh M, Zoler E, Harari D, Chiaravalli J, Meyer B, Rudich Y, Li C, Marton I, Dym O, Elad N, Lewis MG, Andersen H, Gagne M, Seder RA, Douek DC, Schreiber G. Nat Microbiol 6 1188-1198 (2021)
  3. Selectivity determinants of GPCR-G-protein binding. Flock T, Hauser AS, Lund N, Gloriam DE, Balaji S, Babu MM. Nature 545 317-322 (2017)
  4. Protein-protein interaction hotspots carved into sequences. Ofran Y, Rost B. PLoS Comput Biol 3 e119 (2007)
  5. Letter Predicting free energy changes using structural ensembles. Benedix A, Becker CM, de Groot BL, Caflisch A, Böckmann RA. Nat Methods 6 3-4 (2009)
  6. SKEMPI: a Structural Kinetic and Energetic database of Mutant Protein Interactions and its use in empirical models. Moal IH, Fernández-Recio J. Bioinformatics 28 2600-2607 (2012)
  7. Exploring "one-shot" kinetics and small molecule analysis using the ProteOn XPR36 array biosensor. Bravman T, Bronner V, Lavie K, Notcovich A, Papalia GA, Myszka DG. Anal Biochem 358 281-288 (2006)
  8. Interaction of C1q with IgG1, C-reactive protein and pentraxin 3: mutational studies using recombinant globular head modules of human C1q A, B, and C chains. Roumenina LT, Ruseva MM, Zlatarova A, Ghai R, Kolev M, Olova N, Gadjeva M, Agrawal A, Bottazzi B, Mantovani A, Reid KB, Kishore U, Kojouharova MS. Biochemistry 45 4093-4104 (2006)
  9. Can self-inhibitory peptides be derived from the interfaces of globular protein-protein interactions? London N, Raveh B, Movshovitz-Attias D, Schueler-Furman O. Proteins 78 3140-3149 (2010)
  10. Built-in loops allow versatility in domain-domain interactions: lessons from self-interacting domains. Akiva E, Itzhaki Z, Margalit H. Proc Natl Acad Sci U S A 105 13292-13297 (2008)
  11. SPACE: a suite of tools for protein structure prediction and analysis based on complementarity and environment. Sobolev V, Eyal E, Gerzon S, Potapov V, Babor M, Prilusky J, Edelman M. Nucleic Acids Res 33 W39-43 (2005)
  12. Multiple solvent crystal structures: probing binding sites, plasticity and hydration. Mattos C, Bellamacina CR, Peisach E, Pereira A, Vitkup D, Petsko GA, Ringe D. J Mol Biol 357 1471-1482 (2006)
  13. Structure-activity studies in a family of beta-hairpin protein epitope mimetic inhibitors of the p53-HDM2 protein-protein interaction. Fasan R, Dias RL, Moehle K, Zerbe O, Obrecht D, Mittl PR, Grütter MG, Robinson JA. Chembiochem 7 515-526 (2006)
  14. Predicting the Impact of Missense Mutations on Protein-Protein Binding Affinity. Li M, Petukh M, Alexov E, Panchenko AR. J Chem Theory Comput 10 1770-1780 (2014)
  15. Protein-protein interactions: organization, cooperativity and mapping in a bottom-up Systems Biology approach. Keskin O, Ma B, Rogale K, Gunasekaran K, Nussinov R. Phys Biol 2 S24-35 (2005)
  16. Binding hot spots in the TEM1-BLIP interface in light of its modular architecture. Reichmann D, Cohen M, Abramovich R, Dym O, Lim D, Strynadka NC, Schreiber G. J Mol Biol 365 663-679 (2007)
  17. Hot spot-based design of small-molecule inhibitors for protein-protein interactions. Guo W, Wisniewski JA, Ji H. Bioorg Med Chem Lett 24 2546-2554 (2014)
  18. MultiBind and MAPPIS: webservers for multiple alignment of protein 3D-binding sites and their interactions. Shulman-Peleg A, Shatsky M, Nussinov R, Wolfson HJ. Nucleic Acids Res 36 W260-4 (2008)
  19. Nonnatural protein-protein interaction-pair design by key residues grafting. Liu S, Liu S, Zhu X, Liang H, Cao A, Chang Z, Lai L. Proc Natl Acad Sci U S A 104 5330-5335 (2007)
  20. Conserved modular design of an oxygen sensory/signaling network with species-specific output. Crosson S, McGrath PT, Stephens C, McAdams HH, Shapiro L. Proc Natl Acad Sci U S A 102 8018-8023 (2005)
  21. Electrostatic properties of protein-protein complexes. Kundrotas PJ, Alexov E. Biophys J 91 1724-1736 (2006)
  22. Protein-peptide interactions adopt the same structural motifs as monomeric protein folds. Vanhee P, Stricher F, Baeten L, Verschueren E, Lenaerts T, Serrano L, Rousseau F, Schymkowitz J. Structure 17 1128-1136 (2009)
  23. HotRegion: a database of predicted hot spot clusters. Cukuroglu E, Gursoy A, Keskin O. Nucleic Acids Res 40 D829-33 (2012)
  24. Long-range cooperative binding effects in a T cell receptor variable domain. Moza B, Buonpane RA, Zhu P, Herfst CA, Rahman AK, McCormick JK, Kranz DM, Sundberg EJ. Proc Natl Acad Sci U S A 103 9867-9872 (2006)
  25. Photocontrollable peptide-based switches target the anti-apoptotic protein Bcl-xL. Kneissl S, Loveridge EJ, Williams C, Crump MP, Allemann RK. Chembiochem 9 3046-3054 (2008)
  26. High affinity antigen recognition of the dual specific variants of herceptin is entropy-driven in spite of structural plasticity. Bostrom J, Haber L, Koenig P, Kelley RF, Fuh G. PLoS One 6 e17887 (2011)
  27. One target-two different binding modes: structural insights into gevokizumab and canakinumab interactions to interleukin-1β. Blech M, Peter D, Fischer P, Bauer MM, Hafner M, Zeeb M, Nar H. J Mol Biol 425 94-111 (2013)
  28. Restricted mobility of conserved residues in protein-protein interfaces in molecular simulations. Yogurtcu ON, Erdemli SB, Nussinov R, Turkay M, Keskin O. Biophys J 94 3475-3485 (2008)
  29. Revisiting the Voronoi description of protein-protein interfaces. Cazals F, Proust F, Bahadur RP, Janin J. Protein Sci 15 2082-2092 (2006)
  30. SORTCERY-A High-Throughput Method to Affinity Rank Peptide Ligands. Reich LL, Dutta S, Keating AE. J Mol Biol 427 2135-2150 (2015)
  31. Spatial chemical conservation of hot spot interactions in protein-protein complexes. Shulman-Peleg A, Shatsky M, Nussinov R, Wolfson HJ. BMC Biol 5 43 (2007)
  32. Tradeoff between stability and multispecificity in the design of promiscuous proteins. Fromer M, Shifman JM. PLoS Comput Biol 5 e1000627 (2009)
  33. Structural basis of T-cell specificity and activation by the bacterial superantigen TSST-1. Moza B, Varma AK, Buonpane RA, Zhu P, Herfst CA, Nicholson MJ, Wilbuer AK, Seth NP, Wucherpfennig KW, McCormick JK, Kranz DM, Sundberg EJ. EMBO J 26 1187-1197 (2007)
  34. Changes in quaternary structure in the signaling mechanisms of PAS domains. Ayers RA, Moffat K. Biochemistry 47 12078-12086 (2008)
  35. Computational redesign of a protein-protein interface for high affinity and binding specificity using modular architecture and naturally occurring template fragments. Potapov V, Reichmann D, Abramovich R, Filchtinski D, Zohar N, Ben Halevy D, Edelman M, Sobolev V, Schreiber G. J Mol Biol 384 109-119 (2008)
  36. Experimental and computational analyses of the energetic basis for dual recognition of immunity proteins by colicin endonucleases. Keeble AH, Joachimiak LA, Maté MJ, Meenan N, Kirkpatrick N, Baker D, Kleanthous C. J Mol Biol 379 745-759 (2008)
  37. Computational redesign of the SHV-1 beta-lactamase/beta-lactamase inhibitor protein interface. Reynolds KA, Hanes MS, Thomson JM, Antczak AJ, Berger JM, Bonomo RA, Kirsch JF, Handel TM. J Mol Biol 382 1265-1275 (2008)
  38. Energetic determinants of protein binding specificity: insights into protein interaction networks. Carbonell P, Nussinov R, del Sol A. Proteomics 9 1744-1753 (2009)
  39. Fruitful and futile encounters along the association reaction between proteins. Harel M, Spaar A, Schreiber G. Biophys J 96 4237-4248 (2009)
  40. New insight into long-range nonadditivity within protein double-mutant cycles. Istomin AY, Gromiha MM, Vorov OK, Jacobs DJ, Livesay DR. Proteins 70 915-924 (2008)
  41. On the dynamic nature of the transition state for protein-protein association as determined by double-mutant cycle analysis and simulation. Harel M, Cohen M, Schreiber G. J Mol Biol 371 180-196 (2007)
  42. Insights into positive and negative requirements for protein-protein interactions by crystallographic analysis of the beta-lactamase inhibitory proteins BLIP, BLIP-I, and BLP. Gretes M, Lim DC, de Castro L, Jensen SE, Kang SG, Lee KJ, Strynadka NC. J Mol Biol 389 289-305 (2009)
  43. Predicting kinetic constants of protein-protein interactions based on structural properties. Bai H, Yang K, Yu D, Zhang C, Chen F, Lai L. Proteins 79 720-734 (2011)
  44. Structural and biochemical characterization of the interaction between KPC-2 beta-lactamase and beta-lactamase inhibitor protein. Hanes MS, Jude KM, Berger JM, Bonomo RA, Handel TM. Biochemistry 48 9185-9193 (2009)
  45. Binding hot spot in the weak protein complex of physiological redox partners yeast cytochrome C and cytochrome C peroxidase. Volkov AN, Bashir Q, Worrall JA, Ubbink M. J Mol Biol 385 1003-1013 (2009)
  46. Shelling the Voronoi interface of protein-protein complexes reveals patterns of residue conservation, dynamics, and composition. Bouvier B, Grünberg R, Nilges M, Cazals F. Proteins 76 677-692 (2009)
  47. Structural basis of affinity maturation and intramolecular cooperativity in a protein-protein interaction. Cho S, Swaminathan CP, Yang J, Kerzic MC, Guan R, Kieke MC, Kranz DM, Mariuzza RA, Sundberg EJ. Structure 13 1775-1787 (2005)
  48. Aromatic residues link binding and function of intrinsically disordered proteins. Espinoza-Fonseca LM. Mol Biosyst 8 237-246 (2012)
  49. Small-Molecule Inhibitors of the SOX18 Transcription Factor. Fontaine F, Overman J, Moustaqil M, Mamidyala S, Salim A, Narasimhan K, Prokoph N, Robertson AAB, Lua L, Alexandrov K, Koopman P, Capon RJ, Sierecki E, Gambin Y, Jauch R, Cooper MA, Zuegg J, Francois M. Cell Chem Biol 24 346-359 (2017)
  50. Survey of the geometric association of domain-domain interfaces. Kim WK, Ison JC. Proteins 61 1075-1088 (2005)
  51. Modular architecture of nucleotide-binding pockets. Gherardini PF, Ausiello G, Russell RB, Russell RB, Helmer-Citterich M. Nucleic Acids Res 38 3809-3816 (2010)
  52. Protein-protein docking with binding site patch prediction and network-based terms enhanced combinatorial scoring. Gong X, Wang P, Yang F, Chang S, Liu B, He H, Cao L, Xu X, Li C, Chen W, Wang C. Proteins 78 3150-3155 (2010)
  53. Docking of antizyme to ornithine decarboxylase and antizyme inhibitor using experimental mutant and double-mutant cycle data. Cohavi O, Tobi D, Schreiber G. J Mol Biol 390 503-515 (2009)
  54. Roles of residues in the interface of transient protein-protein complexes before complexation. Swapna LS, Bhaskara RM, Sharma J, Srinivasan N. Sci Rep 2 334 (2012)
  55. Analysis of hot region organization in hub proteins. Cukuroglu E, Gursoy A, Keskin O. Ann Biomed Eng 38 2068-2078 (2010)
  56. Four distances between pairs of amino acids provide a precise description of their interaction. Cohen M, Potapov V, Schreiber G. PLoS Comput Biol 5 e1000470 (2009)
  57. The modular organization of domain structures: insights into protein-protein binding. del Sol A, Carbonell P. PLoS Comput Biol 3 e239 (2007)
  58. Characterizing changes in the rate of protein-protein dissociation upon interface mutation using hotspot energy and organization. Agius R, Torchala M, Moal IH, Fernández-Recio J, Bates PA. PLoS Comput Biol 9 e1003216 (2013)
  59. Structural insight into the kinetics and DeltaCp of interactions between TEM-1 beta-lactamase and beta-lactamase inhibitory protein (BLIP). Wang J, Palzkill T, Chow DC. J Biol Chem 284 595-609 (2009)
  60. Low-stringency selection of TEM1 for BLIP shows interface plasticity and selection for faster binders. Cohen-Khait R, Schreiber G. Proc Natl Acad Sci U S A 113 14982-14987 (2016)
  61. The dominance of symmetry in the evolution of homo-oligomeric proteins. Schulz GE. J Mol Biol 395 834-843 (2010)
  62. Crucial importance of the water-entropy effect in predicting hot spots in protein-protein complexes. Oshima H, Yasuda S, Yoshidome T, Ikeguchi M, Kinoshita M. Phys Chem Chem Phys 13 16236-16246 (2011)
  63. Deep geometric representations for modeling effects of mutations on protein-protein binding affinity. Liu X, Luo Y, Li P, Song S, Peng J. PLoS Comput Biol 17 e1009284 (2021)
  64. FlexPepDock lessons from CAPRI peptide-protein rounds and suggested new criteria for assessment of model quality and utility. Marcu O, Dodson EJ, Alam N, Sperber M, Kozakov D, Lensink MF, Schueler-Furman O. Proteins 85 445-462 (2017)
  65. NMR and bioinformatics discovery of exosites that tune metalloelastase specificity for solubilized elastin and collagen triple helices. Palmier MO, Fulcher YG, Bhaskaran R, Duong VQ, Fields GB, Van Doren SR. J Biol Chem 285 30918-30930 (2010)
  66. Remote exosites of the catalytic domain of matrix metalloproteinase-12 enhance elastin degradation. Fulcher YG, Van Doren SR. Biochemistry 50 9488-9499 (2011)
  67. Identification and characterization of beta-lactamase inhibitor protein-II (BLIP-II) interactions with beta-lactamases using phage display. Brown NG, Palzkill T. Protein Eng Des Sel 23 469-478 (2010)
  68. Cluster conservation as a novel tool for studying protein-protein interactions evolution. Rahat O, Yitzhaky A, Schreiber G. Proteins 71 621-630 (2008)
  69. Identification of a β-lactamase inhibitory protein variant that is a potent inhibitor of Staphylococcus PC1 β-lactamase. Yuan J, Chow DC, Huang W, Palzkill T. J Mol Biol 406 730-744 (2011)
  70. Quantification of the transferability of a designed protein specificity switch reveals extensive epistasis in molecular recognition. Melero C, Ollikainen N, Harwood I, Karpiak J, Kortemme T. Proc Natl Acad Sci U S A 111 15426-15431 (2014)
  71. The T cell receptor beta-chain second complementarity determining region loop (CDR2beta governs T cell activation and Vbeta specificity by bacterial superantigens. Nur-ur Rahman AK, Bonsor DA, Herfst CA, Pollard F, Peirce M, Wyatt AW, Kasper KJ, Madrenas J, Sundberg EJ, McCormick JK. J Biol Chem 286 4871-4881 (2011)
  72. A quantitative, real-time assessment of binding of peptides and proteins to gold surfaces. Cohavi O, Reichmann D, Abramovich R, Tesler AB, Bellapadrona G, Kokh DB, Wade RC, Vaskevich A, Rubinstein I, Schreiber G. Chemistry 17 1327-1336 (2011)
  73. Analysis of the binding forces driving the tight interactions between beta-lactamase inhibitory protein-II (BLIP-II) and class A beta-lactamases. Brown NG, Chow DC, Sankaran B, Zwart P, Prasad BV, Palzkill T. J Biol Chem 286 32723-32735 (2011)
  74. Understanding hydrogen-bond patterns in proteins using network motifs. Rahat O, Alon U, Levy Y, Schreiber G. Bioinformatics 25 2921-2928 (2009)
  75. Amino acid substitutions at protein-protein interfaces that modulate the oligomeric state. Nishi H, Ota M. Proteins 78 1563-1574 (2010)
  76. Analysis and network representation of hotspots in protein interfaces using minimum cut trees. Tuncbag N, Salman FS, Keskin O, Gursoy A. Proteins 78 2283-2294 (2010)
  77. Specificity and cooperativity at β-lactamase position 104 in TEM-1/BLIP and SHV-1/BLIP interactions. Hanes MS, Reynolds KA, McNamara C, Ghosh P, Bonomo RA, Kirsch JF, Handel TM. Proteins 79 1267-1276 (2011)
  78. Assessing energetic contributions to binding from a disordered region in a protein-protein interaction . Cho S, Swaminathan CP, Bonsor DA, Kerzic MC, Guan R, Yang J, Kieke MC, Andersen PS, Kranz DM, Mariuzza RA, Sundberg EJ. Biochemistry 49 9256-9268 (2010)
  79. Identification of the β-lactamase inhibitor protein-II (BLIP-II) interface residues essential for binding affinity and specificity for class A β-lactamases. Brown NG, Chow DC, Ruprecht KE, Palzkill T. J Biol Chem 288 17156-17166 (2013)
  80. In proteins, the structural responses of a position to mutation rely on the Goldilocks principle: not too many links, not too few. Dorantes-Gilardi R, Bourgeat L, Pacini L, Vuillon L, Lesieur C. Phys Chem Chem Phys 20 25399-25410 (2018)
  81. Multistability of signal transduction motifs. Saez-Rodriguez J, Hammerle-Fickinger A, Dalal O, Klamt S, Gilles ED, Conradi C. IET Syst Biol 2 80-93 (2008)
  82. Structural basis for specificity and promiscuity in a carrier protein/enzyme system from the sulfur cycle. Grabarczyk DB, Chappell PE, Johnson S, Stelzl LS, Lea SM, Berks BC. Proc Natl Acad Sci U S A 112 E7166-75 (2015)
  83. Activity Mapping the Acyl Carrier Protein: Elongating Ketosynthase Interaction in Fatty Acid Biosynthesis. Mindrebo JT, Misson LE, Johnson C, Noel JP, Burkart MD. Biochemistry 59 3626-3638 (2020)
  84. Combinations of affinity-enhancing mutations in a T cell receptor reveal highly nonadditive effects within and between complementarity determining regions and chains. Pierce BG, Haidar JN, Yu Y, Weng Z. Biochemistry 49 7050-7059 (2010)
  85. Crucial roles of single residues in binding affinity, specificity, and promiscuity in the cellulosomal cohesin-dockerin interface. Slutzki M, Reshef D, Barak Y, Haimovitz R, Rotem-Bamberger S, Lamed R, Bayer EA, Schueler-Furman O. J Biol Chem 290 13654-13666 (2015)
  86. Mutations in protein-binding hot-spots on the hub protein Smad3 differentially affect its protein interactions and Smad3-regulated gene expression. Schiro MM, Stauber SE, Peterson TL, Krueger C, Darnell SJ, Satyshur KA, Drinkwater NR, Newton MA, Hoffmann FM. PLoS One 6 e25021 (2011)
  87. PCRPi-DB: a database of computationally annotated hot spots in protein interfaces. Segura J, Fernandez-Fuentes N. Nucleic Acids Res 39 D755-60 (2011)
  88. Thermodynamic additivity of sequence variations: an algorithm for creating high affinity peptides without large libraries or structural information. Greving MP, Belcher PE, Diehnelt CW, Gonzalez-Moa MJ, Emery J, Fu J, Johnston SA, Woodbury NW. PLoS One 5 e15432 (2010)
  89. Cover and spacer insertions: small nonhydrophobic accessories that assist protein oligomerization. Nishi H, Koike R, Ota M. Proteins 79 2372-2379 (2011)
  90. Predicting where small molecules bind at protein-protein interfaces. Walter P, Metzger J, Thiel C, Helms V. PLoS One 8 e58583 (2013)
  91. Engineering Specificity from Broad to Narrow: Design of a β-Lactamase Inhibitory Protein (BLIP) Variant That Exclusively Binds and Detects KPC β-Lactamase. Chow DC, Rice K, Huang W, Atmar RL, Palzkill T. ACS Infect Dis 2 969-979 (2016)
  92. Modeling and fitting protein-protein complexes to predict change of binding energy. Dourado DF, Flores SC. Sci Rep 6 25406 (2016)
  93. Molecular basis of death effector domain chain assembly and its role in caspase-8 activation. Singh N, Hassan A, Bose K. FASEB J 30 186-200 (2016)
  94. Role of β-lactamase residues in a common interface for binding the structurally unrelated inhibitory proteins BLIP and BLIP-II. Fryszczyn BG, Adamski CJ, Brown NG, Rice K, Huang W, Palzkill T. Protein Sci 23 1235-1246 (2014)
  95. Weighted protein residue networks based on joint recurrences between residues. Karain WI, Qaraeen NI. BMC Bioinformatics 16 173 (2015)
  96. Accurate prediction of interfacial residues in two-domain proteins using evolutionary information: implications for three-dimensional modeling. Bhaskara RM, Padhi A, Srinivasan N. Proteins 82 1219-1234 (2014)
  97. Assessment of software methods for estimating protein-protein relative binding affinities. Gonzalez TR, Martin KP, Barnes JE, Patel JS, Ytreberg FM. PLoS One 15 e0240573 (2020)
  98. Characterizing the morphology of protein binding patches. Malod-Dognin N, Bansal A, Cazals F. Proteins 80 2652-2665 (2012)
  99. Exploring additivity effects of double mutations on the binding affinity of protein-protein complexes. Jemimah S, Gromiha MM. Proteins 86 536-547 (2018)
  100. Interactions of Bovine Serum Albumin with Anti-Cancer Compounds Using a ProteOn XPR36 Array Biosensor and Molecular Docking. Zhang L, Cai QY, Cai ZX, Fang Y, Zheng CS, Wang LL, Lin S, Chen DX, Peng J. Molecules 21 E1706 (2016)
  101. Automated clustering of probe molecules from solvent mapping of protein surfaces: new algorithms applied to hot-spot mapping and structure-based drug design. Lerner MG, Meagher KL, Carlson HA. J Comput Aided Mol Des 22 727-736 (2008)
  102. DBAC: a simple prediction method for protein binding hot spots based on burial levels and deeply buried atomic contacts. Li Z, Wong L, Li J. BMC Syst Biol 5 Suppl 1 S5 (2011)
  103. Identification of an anchor residue for CheA-CheY interactions in the chemotaxis system of Escherichia coli. Thakor H, Nicholas S, Porter IM, Hand N, Stewart RC. J Bacteriol 193 3894-3903 (2011)
  104. Local network patterns in protein-protein interfaces. Luo Q, Hamer R, Reinert G, Deane CM. PLoS One 8 e57031 (2013)
  105. Protein residue network analysis reveals fundamental properties of the human coagulation factor VIII. Lopes TJS, Rios R, Nogueira T, Mello RF. Sci Rep 11 12625 (2021)
  106. Role of tyrosine hot-spot residues at the interface of colicin E9 and immunity protein 9: a comparative free energy simulation study. Luitz MP, Zacharias M. Proteins 81 461-468 (2013)
  107. Systematic substitutions at BLIP position 50 result in changes in binding specificity for class A β-lactamases. Adamski CJ, Palzkill T. BMC Biochem 18 2 (2017)
  108. Antibody Binding Selectivity: Alternative Sets of Antigen Residues Entail High-Affinity Recognition. Nominé Y, Choulier L, Travé G, Vernet T, Altschuh D. PLoS One 10 e0143374 (2015)
  109. Computed insight into a peptide inhibitor preventing the induced fit mechanism of MurA enzyme from Pseudomonas aeruginosa. Lima AH, Dos Santos AM, Alves CN, Lameira J. Chem Biol Drug Des 89 599-607 (2017)
  110. Integration of cell-free protein coexpression with an enzyme-linked immunosorbent assay enables rapid analysis of protein-protein interactions directly from DNA. Layton CJ, Hellinga HW. Protein Sci 20 1432-1438 (2011)
  111. Molecular analysis of restriction endonuclease EcoRII from Escherichia coli reveals precise regulation of its enzymatic activity by autoinhibition. Szczepek M, Mackeldanz P, Möncke-Buchner E, Alves J, Krüger DH, Reuter M. Mol Microbiol 72 1011-1021 (2009)
  112. Prediction of Hot Regions in PPIs Based on Improved Local Community Structure Detecting. Xiaoli Lin, Xiaolong Zhang. IEEE/ACM Trans Comput Biol Bioinform 15 1470-1479 (2018)
  113. Tunnel plasticity and quaternary structural integrity of a pentameric protein ring. Woycechowsky KJ, Seebeck FP, Hilvert D. Protein Sci 15 1106-1114 (2006)
  114. A Machine Learning Framework Predicts the Clinical Severity of Hemophilia B Caused by Point-Mutations. Lopes TJS, Nogueira T, Rios R. Front Bioinform 2 912112 (2022)
  115. A tool for calculating binding-site residues on proteins from PDB structures. Hu J, Yan C. BMC Struct Biol 9 52 (2009)
  116. BLIP-II Employs Differential Hotspot Residues To Bind Structurally Similar Staphylococcus aureus PBP2a and Class A β-Lactamases. Adamski CJ, Palzkill T. Biochemistry 56 1075-1084 (2017)
  117. Combining different design strategies for rational affinity maturation of the MICA-NKG2D interface. Henager SH, Hale MA, Maurice NJ, Dunnington EC, Swanson CJ, Peterson MJ, Ban JJ, Culpepper DJ, Davies LD, Sanders LK, McFarland BJ. Protein Sci 21 1396-1402 (2012)
  118. Mapping Protein-Protein Interaction Interface Peptides with Jun-Fos Assisted Phage Display and Deep Sequencing. Huang W, Soeung V, Boragine DM, Palzkill T. ACS Synth Biol 9 1882-1896 (2020)
  119. Studies on amino acid replacement and inhibitory activity of a beta-lactamase inhibitory peptide. Xie L, Xu M, Yang T, Zhu C, Zhu B, Hu Y. Biochemistry (Mosc) 75 336-341 (2010)
  120. Characterization of protomer interfaces in HslV protease; the bacterial homologue of 20S proteasome. Azim MK, Noor S. Protein J 26 213-219 (2007)
  121. THz frequency spectrum of protein-solvent interaction energy using a recurrence plot-based Wiener-Khinchin method. Karain W. Proteins 84 1549-1557 (2016)
  122. Comment The nitty-gritty of protein interactions. Schreiber G. Structure 13 1737-1738 (2005)
  123. Attention network for predicting T-cell receptor-peptide binding can associate attention with interpretable protein structural properties. Koyama K, Hashimoto K, Nagao C, Mizuguchi K. Front Bioinform 3 1274599 (2023)
  124. Computational analyses reveal fundamental properties of the AT structure related to thrombosis. Lopes TJS, Rios RA, Rios TN, Alencar BM, Ferreira MV, Morishita E. Bioinform Adv 3 vbac098 (2023)
  125. Full-scale network analysis reveals properties of the FV protein structure organization. Ferreira-Martins AJ, Castaldoni R, Alencar BM, Ferreira MV, Nogueira T, Rios RA, Lopes TJS. Sci Rep 13 9546 (2023)
  126. Functional mapping of the anti-idiotypic antibody anti-TS1 scFv using site-directed mutagenesis and kinetic analysis. Erlandsson A, Holm P, Jafari R, Stigbrand T, Sundström BE. MAbs 2 662-669 (2010)
  127. Library of binding protein scaffolds (LibBP): a computational platform for selection of binding protein scaffolds. Hong S, Kim D. Bioinformatics 32 1709-1715 (2016)
  128. Protein Engineering in the Design of Protein-Protein Interactions: SARS-CoV-2 Inhibitors as a Test Case. Zahradník J, Schreiber G. Biochemistry 60 3429-3435 (2021)
  129. Using Implicit-Solvent Potentials to Extract Water Contributions to Enthalpy-Entropy Compensation in Biomolecular Associations. Chen S, Wang ZG. J Phys Chem B 127 6825-6832 (2023)