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Modeling and Design of Peptidomimetics to Modulate Protein–Protein Interactions

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Modeling Peptide-Protein Interactions

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1561))

Abstract

We describe a modular approach to identify and inhibit protein–protein interactions (PPIs) that are mediated by protein secondary and tertiary structures with rationally designed peptidomimetics. Our analysis begins with entries of high-resolution complexes in the Protein Data Bank and utilizes conformational sampling, scoring, and design capabilities of advanced biomolecular modeling software to develop peptidomimetics.

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References

  1. Watkins AM, Arora PS (2015) Structure-based inhibition of protein–protein interactions. Eur J Med Chem 94:480–488

    Article  CAS  PubMed  Google Scholar 

  2. Pelay-Gimeno M, Glas A, Koch O, Grossmann TN (2015) Structure-based design of inhibitors of protein–protein interactions: mimicking peptide binding epitopes. Angew Chem Int Ed 54(31):8896–8927

    Article  CAS  Google Scholar 

  3. London N, Raveh B, Schueler-Furman O (2013) Druggable protein–protein interactions—from hot spots to hot segments. Curr Opin Chem Biol 17(6):952–959

    Article  CAS  PubMed  Google Scholar 

  4. Milroy L-G, Grossmann TN, Hennig S, Brunsveld L et al (2014) Modulators of protein–protein interactions. Chem Rev 114(9):4695–4748

    Article  CAS  PubMed  Google Scholar 

  5. Checco JW, Kreitler DF, Thomas NC, Belair DG et al (2015) Targeting diverse protein–protein interaction interfaces with α/β-peptides derived from the Z-domain scaffold. Proc Natl Acad Sci U S A 112(15):4552–4557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Boersma MD, Haase HS, Peterson-Kaufman KJ, Lee EF et al (2012) Evaluation of diverse alpha/beta-backbone patterns for functional alpha-helix mimicry: analogues of the Bim BH3 domain. J Am Chem Soc 134(1):315–323

    Article  CAS  PubMed  Google Scholar 

  7. Azzarito V, Long K, Murphy NS, Wilson AJ (2013) Inhibition of alpha-helix-mediated protein-protein interactions using designed molecules. Nat Chem 5(3):161–173

    Article  CAS  PubMed  Google Scholar 

  8. Walensky LD, Bird GH (2014) Hydrocarbon-stapled peptides: principles, practice, and progress. J Med Chem 57(15):6275–6288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Villar EA, Beglov D, Chennamadhavuni S, Porco JA Jr et al (2014) How proteins bind macrocycles. Nat Chem Biol 10(9):723–731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Arkin Michelle R, Tang Y, Wells James A (2014) Small-molecule inhibitors of protein-protein interactions: progressing toward the reality. Chem Biol 21(9):1102–1114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Negi SS, Schein CH, Oezguen N, Power TD et al (2007) InterProSurf: a web server for predicting interacting sites on protein surfaces. Bioinformatics 23(24):3397–3399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Vangone A, Oliva R, Cavallo L (2012) CONS-COCOMAPS: a novel tool to measure and visualize the conservation of inter-residue contacts in multiple docking solutions. BMC Bioinformatics 13(Suppl 4):S19

    Article  PubMed  PubMed Central  Google Scholar 

  13. Vangone A, Spinelli R, Scarano V, Cavallo L et al (2011) COCOMAPS: a web application to analyze and visualize contacts at the interface of biomolecular complexes. Bioinformatics 27(20):2915–2916

    Article  CAS  PubMed  Google Scholar 

  14. Shingate P, Manoharan M, Sukhwal A, Sowdhamini R (2014) ECMIS: computational approach for the identification of hotspots at protein-protein interfaces. BMC Bioinformatics 15:303

    Article  PubMed  PubMed Central  Google Scholar 

  15. Tuncbag N, Keskin O, Gursoy A (2010) HotPoint: hot spot prediction server for protein interfaces. Nucleic Acids Res 38(Web Server issue):W402–W406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lauck F, Smith CA, Friedland GF, Humphris EL et al (2010) RosettaBackrub—a web server for flexible backbone protein structure modeling and design. Nucleic Acids Res 38(Web Server issue):W569–W575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Meireles LM, Domling AS, Camacho CJ (2010) ANCHOR: a web server and database for analysis of protein-protein interaction binding pockets for drug discovery. Nucleic Acids Res 38(Web Server issue):W407–W411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lyskov S, Chou FC, Conchuir SO, Der BS et al (2013) Serverification of molecular modeling applications: the Rosetta Online Server that Includes Everyone (ROSIE). PLoS One 8(5):e63906

    Article  PubMed  PubMed Central  Google Scholar 

  19. Chivian D, Kim DE, Malmstrom L, Bradley P et al (2003) Automated prediction of CASP-5 structures using the Robetta server. Proteins 53(Suppl 6):524–533

    Article  CAS  PubMed  Google Scholar 

  20. Bergey CM, Watkins AM, Arora PS (2013) HippDB: a database of readily targeted helical protein-protein interactions. Bioinformatics 29(21):2806–2807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bullock BN, Jochim AL, Arora PS (2011) Assessing helical protein interfaces for inhibitor design. J Am Chem Soc 133(36):14220–14223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Jochim AL, Arora PS (2010) Systematic analysis of helical protein interfaces reveals targets for synthetic inhibitors. ACS Chem Biol 5(10):919–923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Jochim AL, Arora PS (2009) Assessment of helical interfaces in protein-protein interactions. Mol Biosyst 5:924–926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Watkins AM, Arora PS (2014) The anatomy of β-strands at protein-protein interfaces. ACS Chem Biol 9(8):1747–1754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Watkins AM, Wuo MG, Arora PS (2015) Protein-protein interactions mediated by helical tertiary structure motifs. J Am Chem Soc 137(36):11622–11630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tosovska P, Arora PS (2010) Oligooxopiperazines as nonpeptidic alpha-helix mimetics. Org Lett 12:1588–1591

    Article  CAS  PubMed  Google Scholar 

  27. Patgiri A, Jochim AL, Arora PS (2008) A hydrogen bond surrogate approach for stabilization of short peptide sequences in alpha-helical conformation. Acc Chem Res 41(10):1289–1300

    Article  CAS  PubMed  Google Scholar 

  28. Jochim AL, Miller SE, Angelo NG, Arora PS (2009) Evaluation of triazolamers as active site inhibitors of HIV-1 protease. Biorg Med Chem Lett 19(21):6023–6026

    Article  CAS  Google Scholar 

  29. Angelo NG, Arora PS (2007) Solution- and solid-phase synthesis of triazole oligomers that display protein-like functionality. J Org Chem 72(21):7963–7967

    Article  CAS  PubMed  Google Scholar 

  30. Angelo NG, Arora PS (2005) Nonpeptidic foldamers from amino acids: synthesis and characterization of 1,3-substituted triazole oligomers. J Am Chem Soc 127:17134–17135

    Article  CAS  PubMed  Google Scholar 

  31. Wuo MG, Mahon AB, Arora PS (2015) An effective strategy for stabilizing minimal coiled coil mimetics. J Am Chem Soc 137(36):11618–11621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Xie X, Piao L, Bullock BN, Smith A et al (2014) Targeting HPV16 E6-p300 interaction reactivates p53 and inhibits the tumorigenicity of HPV-positive head and neck squamous cell carcinoma. Oncogene 33(8):1037–1046

    Article  CAS  PubMed  Google Scholar 

  33. Lao BB, Grishagin I, Mesallati H, Brewer TF et al (2014) In vivo modulation of hypoxia-inducible signaling by topographical helix mimetics. Proc Natl Acad Sci U S A 111(21):7531–7536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lao BB, Drew K, Guarracino DA, Brewer TF et al (2014) Rational design of topographical helix mimics as potent inhibitors of protein-protein interactions. J Am Chem Soc 136(22):7877–7888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kushal S, Lao BB, Henchey LK, Dubey R et al (2013) Protein domain mimetics as in vivo modulators of hypoxia-inducible factor signaling. Proc Natl Acad Sci U S A 110(39):15602–15607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Patgiri A, Yadav KK, Arora PS, Bar-Sagi D (2011) An orthosteric inhibitor of the Ras-Sos interaction. Nat Chem Biol 7(9):585–587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Henchey LK, Porter JR, Ghosh I, Arora PS (2010) High specificity in protein recognition by hydrogen-bond-surrogate alpha-helices: selective inhibition of the p53/MDM2 complex. ChemBiochem 11(15):2104–2107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wang D, Lu M, Arora PS (2008) Inhibition of HIV-1 fusion by hydrogen-bond-surrogate-based alpha helices. Angew Chem Int Ed 47(10):1879–1882

    Article  CAS  Google Scholar 

  39. Wang D, Liao W, Arora PS (2005) Enhanced metabolic stability and protein-binding properties of artificial alpha-helices derived from a hydrogen-bond surrogate: application to Bcl-xL. Angew Chem Int Ed 44:6525–6529

    Article  CAS  Google Scholar 

  40. Leaver-Fay A, Tyka M, Lewis SM, Lange OF et al (2011) ROSETTA3: an object-oriented software suite for the simulation and design of macromolecules. Methods Enzymol 487:545–574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hou T, Wang J, Li Y, Wang W (2011) Assessing the performance of the MM/PBSA and MM/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations. J Chem Inf Model 51(1):69–82

    Article  CAS  PubMed  Google Scholar 

  42. Genheden S, Ryde U (2015) The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert Opin Drug Discov 10(5):449–461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Guerois R, Nielsen JE, Serrano L (2002) Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations. J Mol Biol 320(2):369–387

    Article  CAS  PubMed  Google Scholar 

  44. Kellogg EH, Leaver-Fay A, Baker D (2011) Role of conformational sampling in computing mutation-induced changes in protein structure and stability. Proteins 79(3):830–838

    Article  CAS  PubMed  Google Scholar 

  45. Eisenhaber F, Argos P (1993) Improved strategy in analytic surface calculation for molecular systems: handling of singularities and computational efficiency. J Comput Chem 14(11):1272–1280

    Article  CAS  Google Scholar 

  46. Fraczkiewicz R, Braun W (1998) Exact and efficient analytical calculation of the accessible surface areas and their gradients for macromolecules. J Comput Chem 19(3):319–333

    Article  CAS  Google Scholar 

  47. Kabsch W, Sander C (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22(12):2577–2637

    Article  CAS  PubMed  Google Scholar 

  48. Li Z, Wong L, Li J (2011) DBAC: a simple prediction method for protein binding hot spots based on burial levels and deeply buried atomic contacts. BMC Syst Biol 5(Suppl 1):S5

    Article  CAS  Google Scholar 

  49. Petukh M, Li M, Alexov E (2015) Predicting binding free energy change caused by point mutations with knowledge-modified MM/PBSA method. PLoS Comput Biol 11(7):e1004276

    Article  PubMed  PubMed Central  Google Scholar 

  50. Xin D, Ko E, Perez LM, Ioerger TR et al (2013) Evaluating minimalist mimics by exploring key orientations on secondary structures (EKOS). Org Biomol Chem 11(44):7789–7801

    Article  CAS  PubMed  Google Scholar 

  51. Ko E, Liu J, Burgess K (2011) Minimalist and universal peptidomimetics. Chem Soc Rev 40:4411–4421

    Article  CAS  PubMed  Google Scholar 

  52. Ko E, Liu J, Perez LM, Lu G et al (2010) Universal peptidomimetics. J Am Chem Soc 133(3):462–477

    Article  PubMed  PubMed Central  Google Scholar 

  53. Mahon AB, Miller SE, Joy ST, Arora PS (2012) Rational design strategies for developing synthetic inhibitors of helical protein interfaces protein-protein interactions, vol 8. Springer, New York. doi:10.1007/978-3-642-28965-1_6

    Google Scholar 

  54. Henchey LK, Jochim AL, Arora PS (2008) Contemporary strategies for the stabilization of peptides in the alpha-helical conformation. Curr Opin Chem Biol 12(6):692–697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Freire F, Gellman SH (2011) Macrocyclic design strategies for small, stable parallel beta-sheet scaffolds. J Am Chem Soc 133(31):12318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Harrison RS, Shepherd NE, Hoang HN, Ruiz-Gomez G et al (2010) Downsizing human, bacterial, and viral proteins to short water-stable alpha helices that maintain biological potency. Proc Natl Acad Sci U S A 107(26):11686–11691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Henchey LK, Kushal S, Dubey R, Chapman RN et al (2010) Inhibition of hypoxia inducible factor 1–transcription coactivator interaction by a hydrogen bond surrogate alpha-helix. J Am Chem Soc 132(3):941–943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Lingard H, Han JT, Thompson AL, Leung IKH et al (2014) Diphenylacetylene-linked peptide strands induce bidirectional β-sheet formation. Angew Chem Int Ed 53(14):3650–3653

    Article  CAS  Google Scholar 

  59. Sutherell CL, Thompson S, Scott RTW, Hamilton AD (2012) Aryl-linked imidazolidin-2-ones as non-peptidic [small beta]-strand mimetics. Chem Commun 48(79):9834–9836

    Article  CAS  Google Scholar 

  60. Kang CW, Sun Y, Del Valle JR (2012) Substituted imidazo[1,2-a]pyridines as β-strand peptidomimetics. Org Lett 14(24):6162–6165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Khasanova TV, Khakshoor O, Nowick JS (2008) Functionalized analogues of an unnatural amino acid that mimics a tripeptide Œ ≤ -strand. Org Lett 10(22):5293–5296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Hammond MC, Harris BZ, Lim WA, Bartlett PA (2006) Beta strand peptidomimetics as potent PDZ domain ligands. Chem Biol 13(12):1247–1251

    Article  CAS  PubMed  Google Scholar 

  63. Phillips ST, Rezac M, Abel U, Kossenjans M et al (2002) “@-tides”: the 1,2-dihydro-3(6H)-pyridinone unit as a beta-strand mimic. J Am Chem Soc 124(1):58–66

    Article  CAS  PubMed  Google Scholar 

  64. Tsai JH, Waldman AS, Nowick JS (1999) Two new beta-strand mimics. Bioorg Med Chem 7(1):29–38

    Article  CAS  PubMed  Google Scholar 

  65. Smith AB, Keenan TP, Holcomb RC, Sprengeler PA et al (1992) Design, synthesis, and crystal-structure of a pyrrolinone-based peptidomimetic possessing the conformation of a beta-strand—potential application to the design of novel inhibitors of proteolytic-enzymes. J Am Chem Soc 114(26):10672–10674

    Article  CAS  Google Scholar 

  66. Loughlin WA, Tyndall JDA, Glenn MP, Fairlie DP (2004) Beta-strand mimetics. Chem Rev 104(12):6085–6117

    Article  CAS  PubMed  Google Scholar 

  67. Hawkins PC, Skillman AG, Warren GL, Ellingson BA et al (2010) Conformer generation with OMEGA: algorithm and validation using high quality structures from the Protein Databank and Cambridge Structural Database. J Chem Inf Model 50(4):572–584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Bahar I, Lezon TR, Bakan A, Shrivastava IH (2010) Normal mode analysis of biomolecular structures: functional mechanisms of membrane proteins. Chem Rev 110(3):1463–1497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Fuglebakk E, Echave J, Reuter N (2012) Measuring and comparing structural fluctuation patterns in large protein datasets. Bioinformatics 28(19):2431–2440

    Article  CAS  PubMed  Google Scholar 

  70. Bornot A, Etchebest C, de Brevern AG (2011) Predicting protein flexibility through the prediction of local structures. Proteins 79(3):839–852

    Article  CAS  PubMed  Google Scholar 

  71. Hilser VJ, Whitten ST (2014) Using the COREX/BEST server to model the native-state ensemble. Methods Mol Biol 1084:255–269

    Article  CAS  PubMed  Google Scholar 

  72. Seeliger D, de Groot BL (2010) Conformational transitions upon ligand binding: holo-structure prediction from apo conformations. PLoS Comput Biol 6(1):e1000634

    Article  PubMed  PubMed Central  Google Scholar 

  73. Kortemme T, Kim DE, Baker D (2004) Computational alanine scanning of protein-protein interfaces. Sci STKE 2004(219):pl2

    PubMed  Google Scholar 

  74. Drew K, Renfrew PD, Craven TW, Butterfoss GL et al (2013) Adding diverse noncanonical backbones to rosetta: enabling peptidomimetic design. PLoS One 8(7):e67051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Darnell SJ, LeGault L, Mitchell JC (2008) KFC Server: interactive forecasting of protein interaction hot spots. Nucleic Acids Res 36(Web Server issue):W265–W269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Koes DR, Camacho CJ (2012) PocketQuery: protein-protein interaction inhibitor starting points from protein-protein interaction structure. Nucleic Acids Res 40(Web Server issue):W387–W392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Schmidtke P, Le Guilloux V, Maupetit J, Tuffery P (2010) fpocket: online tools for protein ensemble pocket detection and tracking. Nucleic Acids Res 38(Web Server issue):W582–W589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Rooklin D, Wang C, Katigbak J, Arora PS et al (2015) AlphaSpace: fragment-centric topographical mapping to target protein-protein interaction interfaces. J Chem Inf Model 55(8):1585–1599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Chen J, Ma X, Yuan Y, Pei J et al (2014) Protein-protein interface analysis and hot spots identification for chemical ligand design. Curr Pharm Des 20(8):1192–1200

    Article  CAS  PubMed  Google Scholar 

  80. Frishman D, Argos P (1995) Knowledge-based protein secondary structure assignment. Proteins 23(4):566–579

    Article  CAS  PubMed  Google Scholar 

  81. Lemmon G, Meiler J (2012) Rosetta ligand docking with flexible XML protocols. Methods Mol Biol 819:143–155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Gray JJ, Moughon S, Wang C, Schueler-Furman O et al (2003) Protein-protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations. J Mol Biol 331(1):281–299

    Article  CAS  PubMed  Google Scholar 

  83. Richter F, Leaver-Fay A, Khare SD, Bjelic S et al (2011) De novo enzyme design using Rosetta3. PLoS One 6(5):e19230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Rothlisberger D, Khersonsky O, Wollacott AM, Jiang L et al (2008) Kemp elimination catalysts by computational enzyme design. Nature 453(7192):190–U194

    Article  PubMed  Google Scholar 

  85. Sripakdeevong P, Kladwang W, Das R (2011) An enumerative stepwise ansatz enables atomic-accuracy RNA loop modeling. Proc Natl Acad Sci U S A 108(51):20573–20578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Procacci P, Cardelli C (2014) Fast switching alchemical transformations in molecular dynamics simulations. J Chem Theory Comput 10(7):2813–2823

    Article  CAS  PubMed  Google Scholar 

  87. Meng Y, Dashti DS, Roitberg AE (2011) Computing alchemical free energy differences with Hamiltonian replica exchange molecular dynamics (H-REMD) simulations. J Chem Theory Comput 7(9):2721–2727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hallen MA, Keedy DA, Donald BR (2013) Dead-end elimination with perturbations (DEEPer): a provable protein design algorithm with continuous sidechain and backbone flexibility. Proteins 81(1):18–39

    Article  CAS  PubMed  Google Scholar 

  89. Georgiev I, Donald BR (2007) Dead-end elimination with backbone flexibility. Bioinformatics 23(13):i185–i194

    Article  CAS  PubMed  Google Scholar 

  90. Tidor B (1993) Simulated annealing on free energy surfaces by a combined molecular dynamics and Monte Carlo approach. J Phys Chem 97(5):1069–1073

    Article  CAS  Google Scholar 

  91. Fleishman SJ, Leaver-Fay A, Corn JE, Strauch EM et al (2011) RosettaScripts: a scripting language interface to the Rosetta macromolecular modeling suite. PLoS One 6(6):e20161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Kawatkar S, Wang H, Czerminski R, Joseph-McCarthy D (2009) Virtual fragment screening: an exploration of various docking and scoring protocols for fragments using Glide. J Comput Aided Mol Des 23(8):527–539

    Article  CAS  PubMed  Google Scholar 

  93. Sandor M, Kiss R, Keseru GM (2010) Virtual fragment docking by Glide: a validation study on 190 protein-fragment complexes. J Chem Inf Model 50(6):1165–1172

    Article  CAS  PubMed  Google Scholar 

  94. Lewis SM, Kuhlman BA (2011) Anchored design of protein-protein interfaces. PLoS One 6(6):e20872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Leaver-Fay A, O’Meara MJ, Tyka M, Jacak R et al (2013) Scientific benchmarks for guiding macromolecular energy function improvement. Methods Enzymol 523:109–143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Vanommeslaeghe K, Hatcher E, Acharya C, Kundu S et al (2010) CHARMM general force field: a force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J Comput Chem 31(4):671–690

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Hynninen AP, Crowley MF (2014) New faster CHARMM molecular dynamics engine. J Comput Chem 35(5):406–413

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Chemistry, New York University, New York, NY, USA

    Andrew M. Watkins

  2. Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY, USA

    Richard Bonneau

  3. Computer Science Department, Courant Institute of Mathematical Sciences, New York University, New York, NY, USA

    Richard Bonneau

  4. Department of Chemistry, New York University, 29 Washington Place, Brown Bldg., Room 360, New York, NY, USA

    Paramjit S. Arora

Authors
  1. Andrew M. Watkins
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  2. Richard Bonneau
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  3. Paramjit S. Arora
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Corresponding author

Correspondence to Paramjit S. Arora .

Editor information

Editors and Affiliations

  1. Microbiology and Molecular Genetics, Hebrew University Hadassah Medical School, Jerusalem, Israel

    Ora Schueler-Furman

  2. Organic Chemistry, The Weizmann Institute of Science, Rehovot, Israel

    Nir London

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Watkins, A.M., Bonneau, R., Arora, P.S. (2017). Modeling and Design of Peptidomimetics to Modulate Protein–Protein Interactions. In: Schueler-Furman, O., London, N. (eds) Modeling Peptide-Protein Interactions. Methods in Molecular Biology, vol 1561. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6798-8_17

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  • DOI: https://doi.org/10.1007/978-1-4939-6798-8_17

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