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Design of Monomeric Water-Soluble β-Hairpin and β-Sheet Peptides

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Protein Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1216))

Abstract

Since the first report in 1993 (JACS 115, 5887–5888) of a peptide able to form a monomeric β-hairpin structure in aqueous solution, the design of peptides forming either β-hairpins (two-stranded antiparallel β-sheets) or three-stranded antiparallel β-sheets has become a field of growing interest and activity. These studies have yielded great insights into the principles governing the stability and folding of β-hairpins and antiparallel β-sheets. This chapter provides an overview of the reported β-hairpin/β-sheet peptides focussed on the applied design criteria, reviews briefly the factors contributing to β-hairpin/β-sheet stability, and describes a protocol for the de novo design of β-sheet-forming peptides based on them. Guidelines to select appropriate turn and strand residues and to avoid self-association are provided. The methods employed to check the success of new designed peptides are also summarized. Since NMR is the best technique to that end, NOEs and chemical shifts characteristic of β-hairpins and three-stranded antiparallel β-sheets are given.

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References

  1. Blanco FJ, Jimenez MA, Herranz J, Rico M, Santoro J, Nieto JL (1993) NMR evidence of a short linear peptide that folds into a beta-hairpin in aqueous solution. J Am Chem Soc 115:5887–5888

    CAS  Google Scholar 

  2. Nowick JS (2008) Exploring beta-sheet structure and interactions with chemical model systems. Acc Chem Res 41:1319–1330

    PubMed  CAS  PubMed Central  Google Scholar 

  3. Khakshoor O, Nowick JS (2008) Artificial beta-sheets: chemical models of beta-sheets. Curr Opin Chem Biol 12:722–729

    PubMed  CAS  PubMed Central  Google Scholar 

  4. Freire F, Gellman SH (2009) Macrocyclic design strategies for small, stable parallel beta-sheet scaffolds. J Am Chem Soc 131:7970–7972

    PubMed  CAS  PubMed Central  Google Scholar 

  5. Liang H, Chen H, Fan K, Wei P, Guo X, Jin C et al (2009) De novo design of a beta alpha beta motif. Angew Chem Int Ed Engl 48: 3301–3303

    PubMed  CAS  Google Scholar 

  6. Robinson JA (2008) Beta-hairpin peptidomimetics: design, structures and biological activities. Acc Chem Res 41:1278–1288

    PubMed  CAS  Google Scholar 

  7. Fuller AA, Du D, Liu F, Davoren JE, Bhabha G, Kroon G et al (2009) Evaluating beta-turn mimics as beta-sheet folding nucleators. Proc Natl Acad Sci U S A 106:11067–11072

    PubMed  CAS  PubMed Central  Google Scholar 

  8. Santiveri CM, Jimenez MA (2010) Tryptophan residues: scarce in proteins but strong stabilizers of beta-hairpin peptides. Biopolymers 94: 779–790

    PubMed  CAS  Google Scholar 

  9. Lewandowska A, Oldziej S, Liwo A, Scheraga HA (2010) beta-hairpin-forming peptides; models of early stages of protein folding. Biophys Chem 151:1–9

    PubMed  CAS  PubMed Central  Google Scholar 

  10. Hughes RM, Waters ML (2006) Model systems for beta-hairpins and beta-sheets. Curr Opin Struct Biol 16:514–512

    PubMed  CAS  Google Scholar 

  11. Pantoja-Uceda D, Santiveri CM, Jimenez MA (2006) De novo design of monomeric beta-hairpin and beta-sheet peptides. Methods Mol Biol 340:27–51

    PubMed  CAS  Google Scholar 

  12. Searle MS, Ciani B (2004) Design of β-sheet systems for understanding the thermodynamics and kinetics of protein folding. Curr Opin Struct Biol 14:458–464

    PubMed  CAS  Google Scholar 

  13. Searle MS (2004) Insights into stabilizing weak interactions in designed peptide beta-hairpins. Biopolymers 76:185–195

    PubMed  CAS  Google Scholar 

  14. Stotz CE, Topp EM (2004) Applications of model beta-hairpin peptides. J Pharm Sci 93: 2881–2894

    PubMed  CAS  Google Scholar 

  15. Searle MS (2001) Peptide models of protein β-sheets: design, folding and insights into stabilising weak interactions. J Chem Soc Perkin Trans 2:1011–1020

    Google Scholar 

  16. Venkatraman J, Shankaramma SC, Balaram P (2001) Design of folded peptides. Chem Rev 101:3131–3152

    PubMed  CAS  Google Scholar 

  17. Serrano L (2000) The relationship between sequence and structure in elementary folding units. Adv Protein Chem 53:49–85

    PubMed  CAS  Google Scholar 

  18. Lacroix E, Kortemme T, Lopez de la Paz M, Serrano L (1999) The design of linear peptides that fold as monomeric beta-sheet structures. Curr Opin Struct Biol 9:487–493

    PubMed  CAS  Google Scholar 

  19. Ramirez-Alvarado M, Kortemme T, Blanco FJ, Serrano L (1999) Beta-hairpin and beta-sheet formation in designed linear peptides. Bioorg Med Chem 7:93–103

    PubMed  CAS  Google Scholar 

  20. Blanco F, Ramirez-Alvarado M, Serrano L (1998) Formation and stability of beta-hairpin structures in polypeptides. Curr Opin Struct Biol 8:107–111

    PubMed  CAS  Google Scholar 

  21. Gellman SH (1998) Minimal model systems for beta sheet secondary structure in proteins. Curr Opin Chem Biol 2:717–725

    PubMed  CAS  Google Scholar 

  22. Smith CK, Regan L (1997) Construction and design of beta sheets. Acc Chem Res 30: 153–161

    CAS  Google Scholar 

  23. Richardson JS (1981) The anatomy and taxonomy of protein structure. Adv Protein Chem 34:167–339

    PubMed  CAS  Google Scholar 

  24. Sibanda BL, Blundell TL, Thornton JM (1989) Conformation of beta-hairpins in protein structures. A systematic classification with applications to modelling by homology, electron density fitting and protein engineering. J Mol Biol 206:759–777

    PubMed  CAS  Google Scholar 

  25. Rose GD, Gierasch LM, Smith JA (1985) Turns in peptides and proteins. Adv Protein Chem 37:1–109

    PubMed  CAS  Google Scholar 

  26. Cootes AP, Curmi PM, Cunningham R, Donnelly C, Torda AE (1998) The dependence of amino acid pair correlations on structural environment. Proteins 32:175–189

    PubMed  CAS  Google Scholar 

  27. Blanco FJ, Rivas G, Serrano L (1994) A short linear peptide that folds into a native stable beta-hairpin in aqueous solution. Nat Struct Biol 1:584–590

    PubMed  CAS  Google Scholar 

  28. Skwierawska A, Rodziewicz-Motowidlo S, Oldziej S, Liwo A, Scheraga HA (2008) Conformational studies of the alpha-helical 28-43 fragment of the B3 domain of the immunoglobulin binding protein G from Streptococcus. Biopolymers 89:1032–1044

    PubMed  CAS  PubMed Central  Google Scholar 

  29. Skwierawska A, Makowska J, Oldziej S, Liwo A, Scheraga HA (2009) Mechanism of formation of the C-terminal beta-hairpin of the B3 domain of the immunoglobulin binding protein G from Streptococcus. I. Importance of hydrophobic interactions in stabilization of beta-hairpin structure. Proteins 75:931–953

    PubMed  CAS  PubMed Central  Google Scholar 

  30. Zerella R, Evans PA, Ionides JM, Packman LC, Trotter BW, Mackay JP et al (1999) Autonomous folding of a peptide corresponding to the N-terminal beta-hairpin from ubiquitin. Protein Sci 8:1320–1331

    PubMed  CAS  PubMed Central  Google Scholar 

  31. Mei CG, Jahr N, Singer D, Berger S (2011) Hairpin conformation of an 11-mer peptide. Bioorg Med Chem 19:3497–3501

    PubMed  CAS  Google Scholar 

  32. Hutchinson EG, Thornton JM (1994) A revised set of potentials for beta-turn formation in proteins. Protein Sci 3:2207–2216

    PubMed  CAS  PubMed Central  Google Scholar 

  33. Searle MS, Williams DH, Packman LC (1995) A short linear peptide derived from the N-terminal sequence of ubiquitin folds into a water-stable non-native beta-hairpin. Nat Struct Biol 2:999–1006

    PubMed  CAS  Google Scholar 

  34. Simpson ER, Meldrum JK, Bofill R, Crespo MD, Holmes E, Searle MS (2005) Engineering enhanced protein stability through beta-turn optimization: insights for the design of stable peptide beta-hairpin systems. Angew Chem Int Ed 44:4939–4944

    CAS  Google Scholar 

  35. Haque TS, Gellman SH (1997) Insights into β-hairpin stability in aqueous solution from peptides with enforced type I′ and type II′ β-turns. J Am Chem Soc 119:2303–2304

    CAS  Google Scholar 

  36. Zerella R, Chen PY, Evans PA, Raine A, Williams DH (2000) Structural characterization of a mutant peptide derived from ubiquitin: implications for protein folding. Protein Sci 9:2142–2150

    PubMed  CAS  PubMed Central  Google Scholar 

  37. Chen PY, Gopalacushina BG, Yang CC, Chan SI, Evans PA (2001) The role of a beta-bulge in the folding of the beta-hairpin structure in ubiquitin. Protein Sci 10:2063–2074

    PubMed  CAS  PubMed Central  Google Scholar 

  38. Fesinmeyer RM, Hudson FM, Andersen NH (2004) Enhanced hairpin stability through loop design: the case of the protein G B1 domain hairpin. J Am Chem Soc 126:7238–7243

    PubMed  CAS  Google Scholar 

  39. Espinosa JF, Syud FA, Gellman SH (2005) An autonomously folding beta-hairpin derived from the human YAP65 WW domain: attempts to define a minimum ligand-binding motif. Biopolymers 80:303–311

    PubMed  CAS  Google Scholar 

  40. Carulla N, Woodward C, Barany G (2000) Synthesis and characterization of a beta-hairpin peptide that represents a ‘core module’ of bovine pancreatic trypsin inhibitor (BPTI). Biochemistry 39:7927–7937

    PubMed  CAS  Google Scholar 

  41. Cochran AG, Skelton NJ, Starovasnik MA (2001) Tryptophan zippers: stable, monomeric beta-hairpins. Proc Natl Acad Sci U S A 98: 5578–5583

    PubMed  CAS  PubMed Central  Google Scholar 

  42. Huyghues-Despointes BM, Qu X, Tsai J, Scholtz JM (2006) Terminal ion pairs stabilize the second beta-hairpin of the B1 domain of protein G. Proteins 63:1005–1017

    PubMed  CAS  Google Scholar 

  43. Wei Y, Huyghues-Despointes BM, Tsai J, Scholtz JM (2007) NMR study and molecular dynamics simulations of optimized beta-hairpin fragments of protein G. Proteins 69:285–296

    PubMed  CAS  Google Scholar 

  44. Mirassou Y, Santiveri CM, Perez de Vega MJ, Gonzalez-Muniz R, Jimenez MA (2009) Disulfide bonds versus TrpTrp pairs in irregular beta-hairpins: NMR structure of vammin loop 3-derived peptides as a case study. Chembiochem 10:902–910

    PubMed  CAS  Google Scholar 

  45. Riemen AJ, Waters ML (2008) Stabilization of the N-terminal beta-hairpin of ubiquitin by a terminal hydrophobic cluster. Biopolymers 90: 394–398

    PubMed  CAS  Google Scholar 

  46. Honda S, Yamasaki K, Sawada Y, Morii H (2004) 10 residue folded peptide designed by segment statistics. Structure 12:1507–1518

    PubMed  CAS  Google Scholar 

  47. Honda S, Akiba T, Kato YS, Sawada Y, Sekijima M, Ishimura M et al (2008) Crystal structure of a ten-amino acid protein. J Am Chem Soc 130:15327–15331

    PubMed  CAS  Google Scholar 

  48. Hatfield MP, Murphy RF, Lovas S (2011) The CLN025 decapeptide retains a beta-hairpin conformation in urea and guanidinium chloride. J Phys Chem B 115:4971–4981

    PubMed  CAS  PubMed Central  Google Scholar 

  49. Maynard AJ, Searle MS (1997) NMR structural analysis of a β-hairpin peptide designed for DNA binding. Chem Commun 19:1297–1298

    Google Scholar 

  50. Maynard AJ, Sharman GJ, Searle MS (1998) Origin of β-hairpin stability in solution: structural and thermodynamic analysis of the folding of a model peptide supports hydrophobic stabilization in water. J Am Chem Soc 120: 1996–2007

    CAS  Google Scholar 

  51. Griffiths-Jones SR, Sharman GJ, Maynard AJ, Searle MS (1998) Modulation of intrinsic phi, psi propensities of amino acids by neighbouring residues in the coil regions of protein structures: NMR analysis and dissection of a beta-hairpin peptide. J Mol Biol 284:1597–1609

    PubMed  CAS  Google Scholar 

  52. Griffiths-Jones SR, Maynard AJ, Searle MS (1999) Dissecting the stability of a beta-hairpin peptide that folds in water: NMR and molecular dynamics analysis of the beta-turn and beta-strand contributions to folding. J Mol Biol 292:1051–1069

    PubMed  CAS  Google Scholar 

  53. Searle MS, Griffiths-Jones SR, Skinner-Smith H (1999) Energetics of weak interactions in a β-hairpin peptide: electrostatic and hydrophobic contributions to stability from lysine salt bridges. J Am Chem Soc 121:11615–11620

    CAS  Google Scholar 

  54. Colley CS, Griffiths-Jones SR, George MW, Searle MS (2000) Do interstrand hydrogen bonds contribute to b-hairpin stability in solution? IR analysis of peptide folding in water. Chem Commun 7:593–594

    Google Scholar 

  55. Ciani B, Jourdan M, Searle MS (2003) Stabilization of beta-hairpin peptides by salt bridges: role of preorganization in the energetic contribution of weak interactions. J Am Chem Soc 125:9038–9047

    PubMed  CAS  Google Scholar 

  56. Gokhale A, Weldeghiorghis TK, Taneja V, Satyanarayanajois SD (2011) Conformationally constrained peptides from CD2 to modulate protein–protein interactions between CD2 and CD58. J Med Chem 54:5307–5319

    PubMed  CAS  PubMed Central  Google Scholar 

  57. de Alba E, Jimenez MA, Rico M, Nieto JL (1996) Conformational investigation of designed short linear peptides able to fold into beta-hairpin structures in aqueous solution. Fold Des 1:133–144

    PubMed  Google Scholar 

  58. Ramirez-Alvarado M, Blanco FJ, Serrano L (1996) De novo design and structural analysis of a model beta-hairpin peptide system. Nat Struct Biol 3:604–612

    PubMed  CAS  Google Scholar 

  59. de Alba E, Jimenez MA, Rico M (1997) Turn residue sequence determines beta-hairpin conformation in designed peptides. J Am Chem Soc 119:175–183

    Google Scholar 

  60. de Alba E, Rico M, Jimenez MA (1997) Cross-strand side-chain interactions versus turn conformation in beta-hairpins. Protein Sci 6: 2548–2560

    PubMed  PubMed Central  Google Scholar 

  61. de Alba E, Rico M, Jimenez MA (1999) The turn sequence directs beta-strand alignment in designed beta-hairpins. Protein Sci 8: 2234–2244

    PubMed  PubMed Central  Google Scholar 

  62. Santiveri CM, Rico M, Jimenez MA (2000) Position effect of cross-strand side-chain interactions on β-hairpin formation. Protein Sci 9: 2151–2160

    PubMed  CAS  PubMed Central  Google Scholar 

  63. Santiveri CM, Santoro J, Rico M, Jimenez MA (2002) Thermodynamic analysis of β-hairpin-forming peptides from the thermal dependence of 1H NMR chemical shifts. J Am Chem Soc 124:14903–14909

    PubMed  CAS  Google Scholar 

  64. Santiveri CM, Pantoja-Uceda D, Rico M, Jimenez MA (2005) Beta-hairpin formation in aqueous solution and in the presence of trifluoroethanol: a 1H and 13C nuclear magnetic resonance conformational study of designed peptides. Biopolymers 79:150–162

    Google Scholar 

  65. Santiveri CM, Leon E, Rico M, Jimenez MA (2008) Context-dependence of the contribution of disulfide bonds to beta-hairpin stability. Chemistry 14:488–499

    PubMed  CAS  Google Scholar 

  66. Ramirez-Alvarado M, Blanco FJ, Niemann H, Serrano L (1997) Role of beta-turn residues in beta-hairpin formation and stability in designed peptides. J Mol Biol 273:898–912

    PubMed  CAS  Google Scholar 

  67. Ramirez-Alvarado M, Blanco FJ, Serrano L (2001) Elongation of the BH8 beta-hairpin peptide: electrostatic interactions in beta-hairpin formation and stability. Protein Sci 10: 1381–1392

    PubMed  CAS  PubMed Central  Google Scholar 

  68. Pastor MT, Lopez de la Paz M, Lacroix E, Serrano L, Perez-Paya E (2002) Combinatorial approaches: a new tool to search for highly structured beta-hairpin peptides. Proc Natl Acad Sci U S A 99:614–619

    PubMed  CAS  PubMed Central  Google Scholar 

  69. Pastor MT, Gimenez-Giner A, Perez-Paya E (2005) The role of an aliphatic-aromatic interaction in the stabilization of a model beta-hairpin peptide. Chembiochem 6:1753–1756

    PubMed  CAS  Google Scholar 

  70. Stanger HE, Gellman SH (1998) Rules for antiparallel β-sheet design:d-Pro-Gly is superior to l-Asn-Gly for β-hairpin nucleation. J Am Chem Soc 120:4236–4237

    CAS  Google Scholar 

  71. Syud FA, Espinosa JF, Gellman SH (1999) NMR-based quantification of beta-sheet populations in aqueous solution through use of reference peptides for the folded and unfolded states. J Am Chem Soc 121:11578–11579

    Google Scholar 

  72. Espinosa JF, Gellman SH (2000) A designed beta-hairpin containing a natural hydrophobic cluster. Angew Chem Int Ed 39:2330–2333

    CAS  Google Scholar 

  73. Syud FA, Stanger HE, Gellman SH (2001) Interstrand side chain–side chain interactions in a designed beta-hairpin: significance of both lateral and diagonal pairings. J Am Chem Soc 123:8667–8677

    PubMed  CAS  Google Scholar 

  74. Espinosa JF, Munoz V, Gellman SH (2001) Interplay between hydrophobic cluster and loop propensity in β-hairpin formation. J Mol Biol 306:397–402

    PubMed  CAS  Google Scholar 

  75. Espinosa JF, Syud FA, Gellman SH (2002) Analysis of the factors that stabilize a designed two-stranded antiparallel beta-sheet. Protein Sci 11:1492–1505

    PubMed  CAS  PubMed Central  Google Scholar 

  76. Stanger HE, Syud FA, Espinosa JF, Giriat I, Muir T, Gellman SH (2001) Length-dependent stability and strand length limits in antiparallel β-sheet secondary structure. Proc Natl Acad Sci U S A 98:12015–12020

    PubMed  CAS  PubMed Central  Google Scholar 

  77. Russell S, Cochran AG (2000) Designing stable β-hairpins: energetics contributions from cross-strand residues. J Am Chem Soc 122: 12600–12601

    CAS  Google Scholar 

  78. Cochran AG, Tong RT, Starovasnik MA, Park EJ, McDowell RS, Theaker JE et al (2001) A minimal peptide scaffold for beta-turn display: optimizing a strand position in disulfide-cyclized beta-hairpins. J Am Chem Soc 123:625–632

    PubMed  CAS  Google Scholar 

  79. Russell SJ, Blandl T, Skelton NJ, Cochran AG (2003) Stability of cyclic beta-hairpins: asymmetric contributions from side chains of a hydrogen-bonded cross-strand residue pair. J Am Chem Soc 125:388–395

    PubMed  CAS  Google Scholar 

  80. Blandl T, Cochran AG, Skelton NJ (2003) Turn stability in beta-hairpin peptides: investigation of peptides containing 3:5 type I G1 bulge turns. Protein Sci 12:237–247

    PubMed  CAS  PubMed Central  Google Scholar 

  81. Takekiyo T, Wu L, Yoshimura Y, Shimizu A, Keiderling TA (2009) Relationship between hydrophobic interactions and secondary structure stability for Trpzip beta-hairpin peptides. Biochemistry 48:1543–1552

    PubMed  CAS  Google Scholar 

  82. Wu L, McElheny D, Huang R, Keiderling TA (2009) Role of tryptophan-tryptophan interactions in Trpzip beta-hairpin formation, structure, and stability. Biochemistry 48:10362–10371

    PubMed  CAS  Google Scholar 

  83. Wu L, McElheny D, Takekiyo T, Keiderling TA (2010) Geometry and efficacy of cross-strand Trp/Trp, Trp/Tyr, and Tyr/Tyr aromatic interaction in a beta-hairpin peptide. Biochemistry 49:4705–4714

    PubMed  CAS  Google Scholar 

  84. Wu L, McElheny D, Setnicka V, Hilario J, Keiderling TA (2012) Role of different beta-turns in beta-hairpin conformation and stability studied by optical spectroscopy. Proteins 80:44–60

    PubMed  CAS  Google Scholar 

  85. Andersen NH, Olsen KA, Fesinmeyer RM, Tan X, Hudson FM, Eidenschink LA et al (2006) Minimization and optimization of designed beta-hairpin folds. J Am Chem Soc 128: 6101–6110

    PubMed  CAS  PubMed Central  Google Scholar 

  86. Kier BL, Andersen NH (2008) Probing the lower size limit for protein-like fold stability: ten-residue microproteins with specific, rigid structures in water. J Am Chem Soc 130: 14675–14683

    PubMed  CAS  PubMed Central  Google Scholar 

  87. Eidenschink L, Kier BL, Huggins KN, Andersen NH (2009) Very short peptides with stable folds: building on the interrelationship of Trp/Trp, Trp/cation, and Trp/backbone-amide interaction geometries. Proteins 75:308–322

    PubMed  CAS  PubMed Central  Google Scholar 

  88. Eidenschink L, Crabbe E, Andersen NH (2009) Terminal sidechain packing of a designed beta-hairpin influences conformation and stability. Biopolymers 91:557–564

    PubMed  CAS  PubMed Central  Google Scholar 

  89. Kier BL, Shu I, Eidenschink LA, Andersen NH (2010) Stabilizing capping motif for beta-hairpins and sheets. Proc Natl Acad Sci U S A 107:10466–10471

    PubMed  CAS  PubMed Central  Google Scholar 

  90. Tatko CD, Waters ML (2002) Selective aromatic interactions in beta-hairpin peptides. J Am Chem Soc 124:9372–9373

    PubMed  CAS  Google Scholar 

  91. Tatko CD, Waters ML (2003) The geometry and efficacy of cation-pi interactions in a diagonal position of a designed beta-hairpin. Protein Sci 12:2443–2452

    PubMed  CAS  PubMed Central  Google Scholar 

  92. Kiehna SE, Waters ML (2003) Sequence dependence of beta-hairpin structure: comparison of a salt bridge and an aromatic interaction. Protein Sci 12:2657–2667

    PubMed  CAS  PubMed Central  Google Scholar 

  93. Tatko CD, Waters ML (2004) Investigation of the nature of the methionine-pi interaction in beta-hairpin peptide model systems. Protein Sci 13:2515–2522

    PubMed  CAS  PubMed Central  Google Scholar 

  94. Tatko CD, Waters ML (2004) Comparison of C-H…pi and hydrophobic interactions in a beta-hairpin peptide: impact on stability and specificity. J Am Chem Soc 126:2028–2034

    PubMed  CAS  Google Scholar 

  95. Tatko CD, Waters ML (2004) Effect of halogenation on edge-face aromatic interactions in a beta-hairpin peptide: enhanced affinity with iodo-substituents. Org Lett 6:3969–3972

    PubMed  CAS  Google Scholar 

  96. Riemen AJ, Waters ML (2009) Controlling peptide folding with repulsive interactions between phosphorylated amino acids and tryptophan. J Am Chem Soc 131:14081–14087

    PubMed  CAS  PubMed Central  Google Scholar 

  97. Riemen AJ, Waters ML (2010) Positional effects of phosphoserine on beta-hairpin stability. Org Biomol Chem 8:5411–5417

    PubMed  CAS  Google Scholar 

  98. Meyer D, Mutschler C, Robertson I, Batt A, Tatko C (2013) Aromatic interactions with naphthylalanine in a beta-hairpin peptide. J Pept Sci 19:277–282

    PubMed  CAS  Google Scholar 

  99. Vriend G (1990) WHAT IF: a molecular modeling and drug design program. J Mol Graph 8:52–56

    PubMed  CAS  Google Scholar 

  100. Kortemme T, Ramirez-Alvarado M, Serrano L (1998) Design of a 20-amino acid, three-stranded beta-sheet protein. Science 281: 253–256

    PubMed  CAS  Google Scholar 

  101. Schenck HL, Gellman SH (1998) Use of a designed triple-stranded antiparallel β-sheet to probe β-sheet cooperativity in aqueous solution. J Am Chem Soc 120:4869–4870

    CAS  Google Scholar 

  102. Sharman GJ, Searle MS (1998) Cooperative interaction between the three strands of a designed antiparallel beta-sheet. J Am Chem Soc 120:5291–5300

    CAS  Google Scholar 

  103. de Alba E, Santoro J, Rico M, Jimenez MA (1999) De novo design of a monomeric three-stranded antiparallel beta-sheet. Protein Sci 8:854–865

    PubMed  PubMed Central  Google Scholar 

  104. Fasman GD (1989) The development of the prediction of protein structure. In: Fasman GD (ed) Prediction of protein structure and the principles of protein conformation. Plenum, New York, NY, pp 193–316

    Google Scholar 

  105. Kim CA, Berg JM (1993) Thermodynamic beta-sheet propensities measured using a zinc-finger host peptide. Nature 362:267–270

    PubMed  CAS  Google Scholar 

  106. Minor DL Jr, Kim PS (1994) Context is a major determinant of beta-sheet propensity. Nature 371:264–267

    PubMed  CAS  Google Scholar 

  107. Minor DL Jr, Kim PS (1994) Measurement of the beta-sheet-forming propensities of amino acids. Nature 367:660–663

    PubMed  CAS  Google Scholar 

  108. Smith CK, Withka JM, Regan L (1994) A thermodynamic scale for the beta-sheet forming tendencies of the amino acids. Biochemistry 33:5510–5517

    PubMed  CAS  Google Scholar 

  109. Street AG, Mayo SL (1999) Intrinsic beta-sheet propensities result from van der Waals interactions between side chains and the local backbone. Proc Natl Acad Sci U S A 96: 9074–9076

    PubMed  CAS  PubMed Central  Google Scholar 

  110. Lopez de la Paz M, Lacroix E, Ramirez-Alvarado M, Serrano L (2001) Computer-aided design of beta-sheet peptides. J Mol Biol 312:229–246

    PubMed  CAS  Google Scholar 

  111. Fernandez-Escamilla AM, Ventura S, Serrano L, Jimenez MA (2006) Design and NMR conformational study of a beta-sheet peptide based on Betanova and WW domains. Protein Sci 15:2278–2289

    PubMed  CAS  PubMed Central  Google Scholar 

  112. Santiveri CM, Santoro J, Rico M, Jimenez MA (2004) Factors involved in the stability of isolated β-sheets: turn sequence, β-sheet twisting, and hydrophobic surface burial. Protein Sci 13:1134–1147

    PubMed  CAS  PubMed Central  Google Scholar 

  113. Griffiths-Jones SR, Searle MS (2000) Structure, folding, and energetics of cooperative interactions between beta-strands of a de novo designed three-stranded antiparallel beta sheet peptide. J Am Chem Soc 122: 8350–8356

    CAS  Google Scholar 

  114. Butterfield SM, Waters ML (2003) A designed beta-hairpin peptide for molecular recognition of ATP in water. J Am Chem Soc 125: 9580–9581

    PubMed  CAS  Google Scholar 

  115. Butterfield SM, Sweeney MM, Waters ML (2005) The recognition of nucleotides with model beta-hairpin receptors: investigation of critical contacts and nucleotide selectivity. J Org Chem 70:1105–1114

    PubMed  CAS  Google Scholar 

  116. Butterfield SM, Goodman CM, Rotello VM, Waters ML (2004) A peptide flavoprotein mimic: flavin recognition and redox potential modulation in water by a designed beta hairpin. Angew Chem Int Ed 43:724–727

    CAS  Google Scholar 

  117. Butterfield SM, Cooper WJ, Waters ML (2005) Minimalist protein design: a beta-hairpin peptide that binds ssDNA. J Am Chem Soc 127:24–25

    PubMed  CAS  Google Scholar 

  118. Stewart AL, Waters ML (2009) Structural effects on ss- and dsDNA recognition by a beta-hairpin peptide. Chembiochem 10:539–544

    PubMed  CAS  Google Scholar 

  119. Cline LL, Waters ML (2009) Design of a beta-hairpin peptide-intercalator conjugate for simultaneous recognition of single stranded and double stranded regions of RNA. Org Biomol Chem 7:4622–4630

    PubMed  CAS  Google Scholar 

  120. Stewart AL, Park JH, Waters ML (2011) Redesign of a WW domain peptide for selective recognition of single-stranded DNA. Biochemistry 50:2575–2584

    PubMed  CAS  Google Scholar 

  121. Wilger DJ, Park JH, Hughes RM, Cuellar ME, Waters ML (2011) Induced-fit binding of a polyproline helix by a beta-hairpin peptide. Angew Chem Int Ed 50:12201–12204

    CAS  Google Scholar 

  122. Platt GW, Chung C-W, Searle MS (2001) Design of histidin-Zn2+ binding sites within a β-hairpin peptide: enhancement of β-sheet stability through metal complexation. Chem Commun 13:1162–1163

    Google Scholar 

  123. Ramadan D, Cline DJ, Bai S, Thorpe C, Schneider JP (2007) Effects of As(III) binding on beta-hairpin structure. J Am Chem Soc 129:2981–2988

    PubMed  CAS  Google Scholar 

  124. Maestro B, Santiveri CM, Jimenez MA, Sanz JM (2011) Structural autonomy of a beta-hairpin peptide derived from the pneumococcal choline-binding protein LytA. Protein Eng Des Sel 24:113–122

    PubMed  CAS  Google Scholar 

  125. Sibert RS, Josowicz M, Barry BA (2010) Control of proton and electron transfer in de novo designed, biomimetic beta hairpins. ACS Chem Biol 5:1157–1168

    PubMed  CAS  PubMed Central  Google Scholar 

  126. Diana D, Basile A, De Rosa L, Di Stasi R, Auriemma S, Arra C et al (2011) beta-hairpin peptide that targets vascular endothelial growth factor (VEGF) receptors: design, NMR characterization, and biological activity. J Biol Chem 286:41680–41691

    PubMed  CAS  PubMed Central  Google Scholar 

  127. Chen PY, Lin CK, Lee CT, Jan H, Chan SI (2001) Effects of turn residues in directing the formation of the beta-sheet and in the stability of the beta-sheet. Protein Sci 10: 1794–1800

    PubMed  CAS  PubMed Central  Google Scholar 

  128. Santiveri CM, Rico M, Jimenez MA, Pastor MT, Perez-Paya E (2003) Insights into the determinants of β-sheet stability: 1H and 13C NMR conformational investigation of three-stranded antiparallel β-sheet-forming peptides. J Pept Res 61:177–188

    PubMed  CAS  Google Scholar 

  129. Merkel JS, Regan L (1998) Aromatic rescue of glycine in beta sheets. Fold Des 3: 449–455

    PubMed  CAS  Google Scholar 

  130. Syud FA, Stanger HE, Mortell HS, Espinosa JF, Fisk JD, Fry CG et al (2003) Influence of strand number on antiparallel beta-sheet stability in designed three- and four-stranded beta-sheets. J Mol Biol 326:553–568

    PubMed  CAS  Google Scholar 

  131. de Alba E, Blanco FJ, Jimenez MA, Rico M, Nieto JL (1995) Interactions responsible for the pH dependence of the beta-hairpin conformational population formed by a designed linear peptide. Eur J Biochem 233:283–292

    PubMed  CAS  Google Scholar 

  132. Dhanasekaran M, Prakash O, Gong YX, Baures PW (2004) Expected and unexpected results from combined beta-hairpin design elements. Org Biomol Chem 2:2071–2082

    PubMed  CAS  Google Scholar 

  133. Santiveri CM, Perez de Vega MJ, Gonzalez-Muniz R, Jimenez MA (2011) Trp-Trp pairs as beta-hairpin stabilisers: hydrogen-bonded versus non-hydrogen-bonded sites. Org Biomol Chem 9:5487–5492

    PubMed  CAS  Google Scholar 

  134. Kobayashi N, Honda S, Yoshii H, Munekata E (2000) Role of side-chains in the cooperative beta-hairpin folding of the short C-terminal fragment derived from streptococcal protein G. Biochemistry 39:6564–6571

    PubMed  CAS  Google Scholar 

  135. Phillips ST, Piersanti G, Bartlett PA (2005) Quantifying amino acid conformational preferences and side-chain-side-chain interactions in beta-hairpins. Proc Natl Acad Sci U S A 102:13737–13742

    PubMed  CAS  PubMed Central  Google Scholar 

  136. Hughes RM, Waters ML (2006) Arginine methylation in a beta-hairpin peptide: implications for Arg-pi interactions, DeltaCp(o), and the cold denatured state. J Am Chem Soc 128:12735–12742

    PubMed  CAS  Google Scholar 

  137. Riemen AJ, Waters ML (2009) Design of highly stabilized beta-hairpin peptides through cation-pi interactions of lysine and n-methyllysine with an aromatic pocket. Biochemistry 48:1525–1531

    PubMed  CAS  PubMed Central  Google Scholar 

  138. Hughes RM, Waters ML (2005) Influence of N-methylation on a cation-pi interaction produces a remarkably stable beta-hairpin peptide. J Am Chem Soc 127:6518–6519

    PubMed  CAS  Google Scholar 

  139. Betz SF (1993) Disulfide bonds and the stability of globular proteins. Protein Sci 2:1551–1558

    PubMed  CAS  PubMed Central  Google Scholar 

  140. Pace C (1990) Conformational stability of globular proteins. Trends Biochem Sci 15: 14–17

    PubMed  CAS  Google Scholar 

  141. Pace C, Grimsley G, Thomson B, Barnett J (1988) Conformational stability and activity of ribonuclease T1 with zero, one, and two intact disulfide bonds. J Biol Chem 263: 11820–11825

    PubMed  CAS  Google Scholar 

  142. Andreu D, Rivas L (1998) Animal antimicrobial peptides: an overview. Biopolymers 47: 415–433

    PubMed  CAS  Google Scholar 

  143. Wouters MA, Curmi PM (1995) An analysis of side chain interactions and pair correlations within antiparallel beta-sheets: the differences between backbone hydrogen-bonded and non-hydrogen-bonded residue pairs. Proteins 22:119–131

    PubMed  CAS  Google Scholar 

  144. Hutchinson EG, Sessions RB, Thornton JM, Woolfson DN (1998) Determinants of strand register in antiparallel beta-sheets of proteins. Protein Sci 7:2287–2300

    PubMed  CAS  PubMed Central  Google Scholar 

  145. Gunasekaran K, Ramakrishnan C, Balaram P (1997) β-Hairpins in proteins revisited: lessons for de novo design. Protein Eng 10: 1131–1141

    PubMed  CAS  Google Scholar 

  146. Garcia-Aranda MI, Mirassou Y, Gautier B, Martin-Martinez M, Inguimbert N, Vidal M et al (2011) Disulfide and amide-bridged cyclic peptide analogues of the VEGF(81–91) fragment: synthesis, conformational analysis and biological evaluation. Bioorg Med Chem 19:7526–7533

    PubMed  CAS  Google Scholar 

  147. Park JH, Waters ML (2013) Positional effects of click cyclization on beta-hairpin structure, stability, and function. Org Biomol Chem 11: 69–77

    PubMed  CAS  PubMed Central  Google Scholar 

  148. Celentano V, Diana D, De Rosa L, Romanelli A, Fattorusso R, D’Andrea LD (2012) beta-Hairpin stabilization through an interstrand triazole bridge. Chem Commun 48:762–764

    CAS  Google Scholar 

  149. Arrondo JL, Blanco FJ, Serrano L, Goni FM (1996) Infrared evidence of a beta-hairpin peptide structure in solution. FEBS Lett 384: 35–37

    PubMed  CAS  Google Scholar 

  150. Jourdan M, Griffiths-Jones SR, Searle MS (2000) Folding of a beta-hairpin peptide derived from the N-terminus of ubiquitin. Conformational preferences of beta-turn residues dictate non-native beta-strand interactions. Eur J Biochem 267:3539–3548

    PubMed  CAS  Google Scholar 

  151. Stotz CE, Borchardt RT, Middaugh CR, Siahaan TJ, Vander Velde D, Topp EM (2004) Secondary structure of a dynamic type I′ beta-hairpin peptide. J Pept Res 63:371–382

    PubMed  CAS  Google Scholar 

  152. Fesinmeyer RM, Hudson FM, Olsen KA, White GW, Euser A, Andersen NH (2005) Chemical shifts provide fold populations and register of beta hairpins and beta sheets. J Biomol NMR 33:213–231

    PubMed  CAS  Google Scholar 

  153. Searle MS, Zerella R, Williams DH, Packman LC (1996) Native-like beta-hairpin structure in an isolated fragment from ferredoxin: NMR and CD studies of solvent effects on the N-terminal 20 residues. Protein Eng 9:559–565

    PubMed  CAS  Google Scholar 

  154. Searle MS, Jourdan M (2000) Templating peptide folding on the surface of a micelle: nucleating the formation of a beta-hairpin. Bioorg Med Chem Lett 10:1139–1142

    PubMed  CAS  Google Scholar 

  155. Lowik DW, Linhardt JG, Adams PJ, van Hest JC (2003) Non-covalent stabilization of a beta-hairpin peptide into liposomes. Org Biomol Chem 1:1827–1829

    PubMed  Google Scholar 

  156. Dempsey CE, Mason PE (2006) Insight into indole interactions from alkali metal chloride effects on a tryptophan zipper beta-hairpin peptide. J Am Chem Soc 128:2762–2763

    PubMed  CAS  Google Scholar 

  157. Penel S, Morrison RG, Dobson PD, Mortishire-Smith RJ, Doig AJ (2003) Length preferences and periodicity in beta-strands. Antiparallel edge beta-sheets are more likely to finish in non-hydrogen bonded rings. Protein Eng 16:957–961

    PubMed  CAS  Google Scholar 

  158. Gibbs AC, Kondejewski LH, Gronwald W, Nip AM, Hodges RS, Sykes BD et al (1998) Unusual beta-sheet periodicity in small cyclic peptides. Nat Struct Biol 5:284–288

    PubMed  CAS  Google Scholar 

  159. Li Y (2011) Recombinant production of antimicrobial peptides in Escherichia coli: a review. Protein Expr Purif 80:260–267

    PubMed  CAS  Google Scholar 

  160. Johnson WCJ (1988) Secondary structure of proteins through circular dichroism. Annu Rev Biophys Biophys Chem 17:145–166

    PubMed  CAS  Google Scholar 

  161. Santiveri CM, Rico M, Jimenez MA (2001) 13Cα and 13Cβ chemical shifts as a tool to delineate β-hairpin structures in peptides. J Biomol NMR 19:331–345

    PubMed  CAS  Google Scholar 

  162. Wuthrich K, Billeter M, Braun W (1984) Polypeptide secondary structure determination by nuclear magnetic resonance observation of short proton-proton distances. J Mol Biol 180:715–740

    PubMed  CAS  Google Scholar 

  163. Wuthrich K (1986) NMR of proteins and nucleic acids. Wiley, New York, NY

    Google Scholar 

  164. Ramirez-Alvarado M, Serrano L, Blanco FJ (1997) Conformational analysis of peptides corresponding to all the secondary structure elements of protein L B1 domain: secondary structure propensities are not conserved in proteins with the same fold. Protein Sci 6: 162–174

    PubMed  CAS  PubMed Central  Google Scholar 

  165. Hughes RM, Waters ML (2006) Effects of lysine acetylation in a beta-hairpin peptide: comparison of an amide-pi and a cation-pi interaction. J Am Chem Soc 128:13586–13591

    PubMed  CAS  Google Scholar 

  166. Honda S, Kobayashi N, Munekata E (2000) Thermodynamics of a beta-hairpin structure: evidence for cooperative formation of folding nucleus. J Mol Biol 295:269–278

    PubMed  CAS  Google Scholar 

  167. Huang R, Wu L, McElheny D, Bour P, Roy A, Keiderling TA (2009) Cross-strand coupling and site-specific unfolding thermodynamics of a trpzip beta-hairpin peptide using 13C isotopic labeling and IR spectroscopy. J Phys Chem B 113:5661–5674

    PubMed  CAS  Google Scholar 

  168. Xu Y, Du D, Oyola R (2011) Infrared study of the stability and folding kinetics of a series of beta-hairpin peptides with a common NPDG turn. J Phys Chem B 115:15332–15338

    PubMed  CAS  PubMed Central  Google Scholar 

  169. Xu Y, Oyola R, Gai F (2003) Infrared study of the stability and folding kinetics of a 15-residue beta-hairpin. J Am Chem Soc 125: 15388–15394

    PubMed  CAS  Google Scholar 

  170. Du D, Zhu Y, Huang CY, Gai F (2004) Understanding the key factors that control the rate of beta-hairpin folding. Proc Natl Acad Sci U S A 101:15915–15920

    PubMed  CAS  PubMed Central  Google Scholar 

  171. Hauser K, Krejtschi C, Huang R, Wu L, Keiderling TA (2008) Site-specific relaxation kinetics of a tryptophan zipper hairpin peptide using temperature-jump IR spectroscopy and isotopic labeling. J Am Chem Soc 130: 2984–2992

    PubMed  CAS  Google Scholar 

  172. Kuznetsov SV, Hilario J, Keiderling TA, Ansari A (2003) Spectroscopic studies of structural changes in two beta-sheet-forming peptides show an ensemble of structures that unfold noncooperatively. Biochemistry 42:4321–4332

    PubMed  CAS  Google Scholar 

  173. Awasthi SK, Raghothama S, Balaram P (1995) A designed beta-hairpin peptide. Biochem Biophys Res Commun 216:375–381

    PubMed  CAS  Google Scholar 

  174. Raghothama SR, Awasthi SK, Balaram P (1998) β-Hairpin nucleation by Pro-Gly β-turns. Comparison of dPro-Gly and lPro-Gly sequences in an apolar octapeptide. J Chem Soc Perkin Trans 2:137–143

    Google Scholar 

  175. Rai R, Raghothama S, Balaram P (2006) Design of a peptide hairpin containing a central three-residue loop. J Am Chem Soc 128: 2675–2681

    PubMed  CAS  Google Scholar 

  176. Mahalakshmi R, Raghothama S, Balaram P (2006) NMR analysis of aromatic interactions in designed peptide beta-hairpins. J Am Chem Soc 128:1125–1138

    PubMed  CAS  Google Scholar 

  177. Karle IL, Awasthi SK, Balaram P (1996) A designed beta-hairpin peptide in crystals. Proc Natl Acad Sci U S A 93:8189–8193

    PubMed  CAS  PubMed Central  Google Scholar 

  178. Ottesen JJ, Imperiali B (2001) Design of a discretely folded mini-protein motif with predominantly beta-structure. Nat Struct Biol 8: 535–539

    PubMed  CAS  Google Scholar 

  179. Das C, Raghothama S, Balaram P (1998) A designed three stranded β-sheet peptide as a multiple β-hairpin model. J Am Chem Soc 120:5812–5813

    CAS  Google Scholar 

  180. Das C, Nayak V, Raghothama S, Balaram P (2000) Synthetic protein design: construction of a four-stranded beta-sheet structure and evaluation of its integrity in methanol-water systems. J Pept Res 56:307–317

    PubMed  CAS  Google Scholar 

  181. Carulla N, Woodward C, Barany G (2002) BetaCore, a designed water soluble four-stranded antiparallel beta-sheet protein. Protein Sci 11:1539–1551

    PubMed  CAS  PubMed Central  Google Scholar 

  182. Venkatraman J, Naganagowda GA, Sudha R, Balaram P (2001) De novo design of a five-stranded β-sheet anchoring a metal-ion binding site. Chem Commun 24:2660–2661

    Google Scholar 

  183. Venkatraman J, Nagana Gowda GA, Balaram P (2002) Design and construction of an open multistranded beta-sheet polypeptide stabilized by a disulfide bridge. J Am Chem Soc 124:4987–4994

    PubMed  CAS  Google Scholar 

  184. Mayo KH, Ilyina E (1998) A folding pathway for betapep-4 peptide 33mer: from unfolded monomers and beta-sheet sandwich dimers to well-structured tetramers. Protein Sci 7: 358–368

    PubMed  CAS  PubMed Central  Google Scholar 

  185. Meier S, Guthe S, Kiefhaber T, Grzesiek S (2004) Foldon, the natural trimerization domain of T4 fibritin, dissociates into a monomeric A-state form containing a stable beta-hairpin: atomic details of trimer dissociation and local beta-hairpin stability from residual dipolar couplings. J Mol Biol 344:1051–1069

    PubMed  CAS  Google Scholar 

  186. Doig AJ (1997) A three-stranded beta-sheet peptide in aqueous solution containing N-methyl amino acids to prevent aggregation. Chem Commun 22:2153–2154

    Google Scholar 

  187. Jager M, Deechongkit S, Koepf EK, Nguyen H, Gao J, Powers ET et al (2008) Understanding the mechanism of beta-sheet folding from a chemical and biological perspective. Biopolymers 90:751–758

    PubMed  CAS  Google Scholar 

  188. Kaul R, Angeles AR, Jager M, Powers ET, Kelly JW (2001) Incorporating beta-turns and a turn mimetic out of context in loop 1 of the WW domain affords cooperatively folded beta-sheets. J Am Chem Soc 123:5206–5212

    PubMed  CAS  Google Scholar 

  189. Jager M, Dendle M, Fuller AA, Kelly JW (2007) A cross-strand Trp Trp pair stabilizes the hPin1 WW domain at the expense of function. Protein Sci 16:2306–2313

    PubMed  CAS  PubMed Central  Google Scholar 

  190. Rajagopal K, Lamm MS, Haines-Butterick LA, Pochan DJ, Schneider JP (2009) Tuning the pH responsiveness of beta-hairpin peptide folding, self-assembly, and hydrogel material formation. Biomacromolecules 10:2619–2625

    PubMed  CAS  Google Scholar 

  191. Kaur H, Raghava GP (2002) BetaTPred: prediction of beta-TURNS in a protein using statistical algorithms. Bioinformatics 18:498–499

    PubMed  CAS  Google Scholar 

  192. de la Cruz X, Hutchinson EG, Shepherd A, Thornton JM (2002) Toward predicting protein topology: an approach to identifying beta hairpins. Proc Natl Acad Sci U S A 99: 11157–11162

    PubMed  PubMed Central  Google Scholar 

  193. Cline LL, Waters ML (2009) The structure of well-folded beta-hairpin peptides promotes resistance to peptidase degradation. Biopolymers 92:502–507

    PubMed  CAS  Google Scholar 

  194. Hilario J, Kubelka J, Syud FA, Gellman SH, Keiderling TA (2002) Spectroscopic characterization of selected beta- sheet hairpin models. Biopolymers 67:233–236

    PubMed  Google Scholar 

  195. Sharman GJ, Griffiths-Jones SR, Jourdan M, Searle MS (2001) Effects of amino acid phi, psi propensities and secondary structure interactions in modulating H alpha chemical shifts in peptide and protein beta-sheet. J Am Chem Soc 123:12318–12324

    PubMed  CAS  Google Scholar 

  196. Shu I, Stewart JM, Scian M, Kier BL, Andersen NH (2011) beta-Sheet 13C structuring shifts appear only at the H-bonded sites of hairpins. J Am Chem Soc 133:1196–1199

    PubMed  CAS  PubMed Central  Google Scholar 

  197. Villegas ME, Vila JA, Scheraga HA (2007) Effects of side-chain orientation on the 13C chemical shifts of antiparallel beta-sheet model peptides. J Biomol NMR 37:137–146

    PubMed  CAS  Google Scholar 

  198. Olsen KA, Fesinmeyer RM, Stewart JM, Andersen NH (2005) Hairpin folding rates reflect mutations within and remote from the turn region. Proc Natl Acad Sci U S A 102: 15483–15487

    PubMed  CAS  PubMed Central  Google Scholar 

  199. Scian M, Shu I, Olsen KA, Hassam K, Andersen NH (2013) Mutational effects on the folding dynamics of a minimized hairpin. Biochemistry 52:2556–2564

    PubMed  CAS  PubMed Central  Google Scholar 

  200. Davis CM, Xiao S, Raleigh DP, Dyer RB (2012) Raising the speed limit for beta-hairpin formation. J Am Chem Soc 134: 14476–14482

    PubMed  CAS  PubMed Central  Google Scholar 

  201. Munoz V, Thompson PA, Hofrichter J, Eaton WA (1997) Folding dynamics and mechanism of beta-hairpin formation. Nature 390: 196–199

    PubMed  CAS  Google Scholar 

  202. McMillan AW, Kier BL, Shu I, Byrne A, Andersen NH, Parson WW (2013) Fluorescence of tryptophan in designed hairpin and Trp-cage miniproteins: measurements of fluorescence yields and calculations by quantum mechanical molecular dynamics simulations. J Phys Chem B 117:1790–1809

    PubMed  CAS  PubMed Central  Google Scholar 

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Acknowledgements

Financial support from Spanish MINECO (CTQ2011-22514) and Comunidad de Madrid (S2010/BMD-2305) projects is acknowledged.

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    M. Angeles Jiménez

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  1. Department of Chemistry, University of Basel, Switzerland

    Valentin Köhler

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Jiménez, M.A. (2014). Design of Monomeric Water-Soluble β-Hairpin and β-Sheet Peptides. In: Köhler, V. (eds) Protein Design. Methods in Molecular Biology, vol 1216. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1486-9_2

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