Skip to main content
PMC home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 2000 May;9(5):942–955. doi: 10.1110/ps.9.5.942

Synthesis and NMR solution structure of an alpha-helical hairpin stapled with two disulfide bridges.

P Barthe 1, S Rochette 1, C Vita 1, C Roumestand 1
PMCID: PMC2144636  PMID: 10850804

Abstract

Helical coiled-coils and bundles are some of the most common structural motifs found in proteins. Design and synthesis of alpha-helical motifs may provide interesting scaffolds that can be useful as host structures to display functional sites, thus allowing the engineering of novel functional miniproteins. We have synthesized a 38-amino acid peptide, alpha2p8, encompassing the alpha-helical hairpin present in the structure of p8MTCP1, as an alpha-helical scaffold particularly promising for its stability and permissiveness of sequence mutations. The three-dimensional structure of this peptide has been solved using homonuclear two-dimensional NMR techniques at 600 MHz. After sequence specific assignment, a total of 285 distance and 29 dihedral restraints were collected. The solution structure of alpha2p8 is presented as a set of 30 DIANA structures, further refined by restrained molecular dynamics, using simulated annealing protocol with the AMBER force field. The RMSD values for the backbone and all heavy atoms are 0.65+/-0.25 and 1.51+/-0.21 A, respectively. Excised from its protein context, the alpha-hairpin keeps its native structure: an alpha-helical coiled-coil, similar to that found in superhelical structures, with two helices spanning residues 4-16 and 25-36, and linked by a short loop. This motif is stabilized by two interhelical disulfide bridges and several hydrophobic interactions at the helix interface, leaving most of its solvent-exposed surface available for mutation. This alpha-helical hairpin, easily amenable to synthetic chemistry and biological expression system, may represent a stable and versatile scaffold to display new functional sites and peptide libraries.

Full Text

The Full Text of this article is available as a PDF (907.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banner D. W., Kokkinidis M., Tsernoglou D. Structure of the ColE1 rop protein at 1.7 A resolution. J Mol Biol. 1987 Aug 5;196(3):657–675. doi: 10.1016/0022-2836(87)90039-8. [DOI] [PubMed] [Google Scholar]
  2. Barnham K. J., Dyke T. R., Kem W. R., Norton R. S. Structure of neurotoxin B-IV from the marine worm Cerebratulus lacteus: a helical hairpin cross-linked by disulphide bonding. J Mol Biol. 1997 May 23;268(5):886–902. doi: 10.1006/jmbi.1997.0980. [DOI] [PubMed] [Google Scholar]
  3. Barthe P., Chiche L., Declerck N., Delsuc M. A., Lefèvre J. F., Malliavin T., Mispelter J., Stern M. H., Lhoste J. M., Roumestand C. Refined solution structure and backbone dynamics of 15N-labeled C12A-p8MTCP1 studied by NMR relaxation. J Biomol NMR. 1999 Dec;15(4):271–288. doi: 10.1023/a:1008336418418. [DOI] [PubMed] [Google Scholar]
  4. Barthe P., Yang Y. S., Chiche L., Hoh F., Strub M. P., Guignard L., Soulier J., Stern M. H., van Tilbeurgh H., Lhoste J. M. Solution structure of human p8MTCP1, a cysteine-rich protein encoded by the MTCP1 oncogene, reveals a new alpha-helical assembly motif. J Mol Biol. 1997 Dec 19;274(5):801–815. doi: 10.1006/jmbi.1997.1438. [DOI] [PubMed] [Google Scholar]
  5. Bianchi E., Venturini S., Pessi A., Tramontano A., Sollazzo M. High level expression and rational mutagenesis of a designed protein, the minibody. From an insoluble to a soluble molecule. J Mol Biol. 1994 Feb 18;236(2):649–659. doi: 10.1006/jmbi.1994.1174. [DOI] [PubMed] [Google Scholar]
  6. Braisted A. C., Wells J. A. Minimizing a binding domain from protein A. Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5688–5692. doi: 10.1073/pnas.93.12.5688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brunet A. P., Huang E. S., Huffine M. E., Loeb J. E., Weltman R. J., Hecht M. H. The role of turns in the structure of an alpha-helical protein. Nature. 1993 Jul 22;364(6435):355–358. doi: 10.1038/364355a0. [DOI] [PubMed] [Google Scholar]
  8. Bryson J. W., Betz S. F., Lu H. S., Suich D. J., Zhou H. X., O'Neil K. T., DeGrado W. F. Protein design: a hierarchic approach. Science. 1995 Nov 10;270(5238):935–941. doi: 10.1126/science.270.5238.935. [DOI] [PubMed] [Google Scholar]
  9. Chen Y. H., Yang J. T., Chau K. H. Determination of the helix and beta form of proteins in aqueous solution by circular dichroism. Biochemistry. 1974 Jul 30;13(16):3350–3359. doi: 10.1021/bi00713a027. [DOI] [PubMed] [Google Scholar]
  10. Cohen C., Parry D. A. Alpha-helical coiled coils and bundles: how to design an alpha-helical protein. Proteins. 1990;7(1):1–15. doi: 10.1002/prot.340070102. [DOI] [PubMed] [Google Scholar]
  11. Cunningham B. C., Wells J. A. Minimized proteins. Curr Opin Struct Biol. 1997 Aug;7(4):457–462. doi: 10.1016/s0959-440x(97)80107-8. [DOI] [PubMed] [Google Scholar]
  12. Dahiyat B. I., Mayo S. L. De novo protein design: fully automated sequence selection. Science. 1997 Oct 3;278(5335):82–87. doi: 10.1126/science.278.5335.82. [DOI] [PubMed] [Google Scholar]
  13. De Wolf E., Gill R., Geddes S., Pitts J., Wollmer A., Grötzinger J. Solution structure of a mini IGF-1. Protein Sci. 1996 Nov;5(11):2193–2202. doi: 10.1002/pro.5560051106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. DeGrado W. F., Wasserman Z. R., Lear J. D. Protein design, a minimalist approach. Science. 1989 Feb 3;243(4891):622–628. doi: 10.1126/science.2464850. [DOI] [PubMed] [Google Scholar]
  15. Dhalluin C, Wieruszeski J, Lippens G. An Improved Homonuclear TOCSY Experiment with Minimal Water Saturation. J Magn Reson B. 1996 May;111(2):168–170. doi: 10.1006/jmrb.1996.0075. [DOI] [PubMed] [Google Scholar]
  16. Domingues H., Cregut D., Sebald W., Oschkinat H., Serrano L. Rational design of a GCN4-derived mimetic of interleukin-4. Nat Struct Biol. 1999 Jul;6(7):652–656. doi: 10.1038/10706. [DOI] [PubMed] [Google Scholar]
  17. Dunn I. S. Phage display of proteins. Curr Opin Biotechnol. 1996 Oct;7(5):547–553. doi: 10.1016/s0958-1669(96)80060-7. [DOI] [PubMed] [Google Scholar]
  18. Fezoui Y., Weaver D. L., Osterhout J. J. De novo design and structural characterization of an alpha-helical hairpin peptide: a model system for the study of protein folding intermediates. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3675–3679. doi: 10.1073/pnas.91.9.3675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fields C. G., Lloyd D. H., Macdonald R. L., Otteson K. M., Noble R. L. HBTU activation for automated Fmoc solid-phase peptide synthesis. Pept Res. 1991 Mar-Apr;4(2):95–101. [PubMed] [Google Scholar]
  20. Fisch P., Forster A., Sherrington P. D., Dyer M. J., Rabbitts T. H. The chromosomal translocation t(X;14)(q28;q11) in T-cell pro-lymphocytic leukaemia breaks within one gene and activates another. Oncogene. 1993 Dec;8(12):3271–3276. [PubMed] [Google Scholar]
  21. Gentz R., Rauscher F. J., 3rd, Abate C., Curran T. Parallel association of Fos and Jun leucine zippers juxtaposes DNA binding domains. Science. 1989 Mar 31;243(4899):1695–1699. doi: 10.1126/science.2494702. [DOI] [PubMed] [Google Scholar]
  22. Gibney B. R., Mulholland S. E., Rabanal F., Dutton P. L. Ferredoxin and ferredoxin-heme maquettes. Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15041–15046. doi: 10.1073/pnas.93.26.15041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Gibney B. R., Rabanal F., Dutton P. L. Synthesis of novel proteins. Curr Opin Chem Biol. 1997 Dec;1(4):537–542. doi: 10.1016/s1367-5931(97)80050-6. [DOI] [PubMed] [Google Scholar]
  24. Güntert P., Wüthrich K. Improved efficiency of protein structure calculations from NMR data using the program DIANA with redundant dihedral angle constraints. J Biomol NMR. 1991 Nov;1(4):447–456. doi: 10.1007/BF02192866. [DOI] [PubMed] [Google Scholar]
  25. Handel T. M., Williams S. A., DeGrado W. F. Metal ion-dependent modulation of the dynamics of a designed protein. Science. 1993 Aug 13;261(5123):879–885. doi: 10.1126/science.8346440. [DOI] [PubMed] [Google Scholar]
  26. Harbury P. B., Plecs J. J., Tidor B., Alber T., Kim P. S. High-resolution protein design with backbone freedom. Science. 1998 Nov 20;282(5393):1462–1467. doi: 10.1126/science.282.5393.1462. [DOI] [PubMed] [Google Scholar]
  27. Harper E. T., Rose G. D. Helix stop signals in proteins and peptides: the capping box. Biochemistry. 1993 Aug 3;32(30):7605–7609. doi: 10.1021/bi00081a001. [DOI] [PubMed] [Google Scholar]
  28. Hecht M. H., Richardson J. S., Richardson D. C., Ogden R. C. De novo design, expression, and characterization of Felix: a four-helix bundle protein of native-like sequence. Science. 1990 Aug 24;249(4971):884–891. doi: 10.1126/science.2392678. [DOI] [PubMed] [Google Scholar]
  29. Houston M. E., Jr, Campbell A. P., Lix B., Kay C. M., Sykes B. D., Hodges R. S. Lactam bridge stabilization of alpha-helices: the role of hydrophobicity in controlling dimeric versus monomeric alpha-helices. Biochemistry. 1996 Aug 6;35(31):10041–10050. doi: 10.1021/bi952757m. [DOI] [PubMed] [Google Scholar]
  30. Houston M. E., Jr, Gannon C. L., Kay C. M., Hodges R. S. Lactam bridge stabilization of alpha-helical peptides: ring size, orientation and positional effects. J Pept Sci. 1995 Jul-Aug;1(4):274–282. doi: 10.1002/psc.310010408. [DOI] [PubMed] [Google Scholar]
  31. Houston M. E., Jr, Wallace A., Bianchi E., Pessi A., Hodges R. S. Use of a conformationally restricted secondary structural element to display peptide libraries: a two-stranded alpha-helical coiled-coil stabilized by lactam bridges. J Mol Biol. 1996 Sep 20;262(2):270–282. doi: 10.1006/jmbi.1996.0512. [DOI] [PubMed] [Google Scholar]
  32. Hyberts S. G., Goldberg M. S., Havel T. F., Wagner G. The solution structure of eglin c based on measurements of many NOEs and coupling constants and its comparison with X-ray structures. Protein Sci. 1992 Jun;1(6):736–751. doi: 10.1002/pro.5560010606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Hyberts S. G., Märki W., Wagner G. Stereospecific assignments of side-chain protons and characterization of torsion angles in Eglin c. Eur J Biochem. 1987 May 4;164(3):625–635. doi: 10.1111/j.1432-1033.1987.tb11173.x. [DOI] [PubMed] [Google Scholar]
  34. Ilyina E., Roongta V., Mayo K. H. NMR structure of a de novo designed, peptide 33mer with two distinct, compact beta-sheet folds. Biochemistry. 1997 Apr 29;36(17):5245–5250. doi: 10.1021/bi963064o. [DOI] [PubMed] [Google Scholar]
  35. Johnsson K., Allemann R. K., Widmer H., Benner S. A. Synthesis, structure and activity of artificial, rationally designed catalytic polypeptides. Nature. 1993 Oct 7;365(6446):530–532. doi: 10.1038/365530a0. [DOI] [PubMed] [Google Scholar]
  36. Kamtekar S., Schiffer J. M., Xiong H., Babik J. M., Hecht M. H. Protein design by binary patterning of polar and nonpolar amino acids. Science. 1993 Dec 10;262(5140):1680–1685. doi: 10.1126/science.8259512. [DOI] [PubMed] [Google Scholar]
  37. King D. S., Fields C. G., Fields G. B. A cleavage method which minimizes side reactions following Fmoc solid phase peptide synthesis. Int J Pept Protein Res. 1990 Sep;36(3):255–266. doi: 10.1111/j.1399-3011.1990.tb00976.x. [DOI] [PubMed] [Google Scholar]
  38. Kortemme T., Ramírez-Alvarado M., Serrano L. Design of a 20-amino acid, three-stranded beta-sheet protein. Science. 1998 Jul 10;281(5374):253–256. doi: 10.1126/science.281.5374.253. [DOI] [PubMed] [Google Scholar]
  39. Kumar A., Ernst R. R., Wüthrich K. A two-dimensional nuclear Overhauser enhancement (2D NOE) experiment for the elucidation of complete proton-proton cross-relaxation networks in biological macromolecules. Biochem Biophys Res Commun. 1980 Jul 16;95(1):1–6. doi: 10.1016/0006-291x(80)90695-6. [DOI] [PubMed] [Google Scholar]
  40. Kuroda Y., Nakai T., Ohkubo T. Solution structure of a de novo helical protein by 2D-NMR spectroscopy. J Mol Biol. 1994 Feb 25;236(3):862–868. doi: 10.1006/jmbi.1994.1194. [DOI] [PubMed] [Google Scholar]
  41. Landschulz W. H., Johnson P. F., McKnight S. L. The DNA binding domain of the rat liver nuclear protein C/EBP is bipartite. Science. 1989 Mar 31;243(4899):1681–1688. doi: 10.1126/science.2494700. [DOI] [PubMed] [Google Scholar]
  42. Ludvigsen S., Andersen K. V., Poulsen F. M. Accurate measurements of coupling constants from two-dimensional nuclear magnetic resonance spectra of proteins and determination of phi-angles. J Mol Biol. 1991 Feb 20;217(4):731–736. doi: 10.1016/0022-2836(91)90529-f. [DOI] [PubMed] [Google Scholar]
  43. McLachlan A. D., Stewart M. Tropomyosin coiled-coil interactions: evidence for an unstaggered structure. J Mol Biol. 1975 Oct 25;98(2):293–304. doi: 10.1016/s0022-2836(75)80119-7. [DOI] [PubMed] [Google Scholar]
  44. Myszka D. G., Chaiken I. M. Design and characterization of an intramolecular antiparallel coiled coil peptide. Biochemistry. 1994 Mar 8;33(9):2363–2372. doi: 10.1021/bi00175a003. [DOI] [PubMed] [Google Scholar]
  45. Nelson J. W., Kallenbach N. R. Stabilization of the ribonuclease S-peptide alpha-helix by trifluoroethanol. Proteins. 1986 Nov;1(3):211–217. doi: 10.1002/prot.340010303. [DOI] [PubMed] [Google Scholar]
  46. Nord K., Nilsson J., Nilsson B., Uhlén M., Nygren P. A. A combinatorial library of an alpha-helical bacterial receptor domain. Protein Eng. 1995 Jun;8(6):601–608. doi: 10.1093/protein/8.6.601. [DOI] [PubMed] [Google Scholar]
  47. Nygren P. A., Uhlén M. Scaffolds for engineering novel binding sites in proteins. Curr Opin Struct Biol. 1997 Aug;7(4):463–469. doi: 10.1016/s0959-440x(97)80108-x. [DOI] [PubMed] [Google Scholar]
  48. O'Shea E. K., Klemm J. D., Kim P. S., Alber T. X-ray structure of the GCN4 leucine zipper, a two-stranded, parallel coiled coil. Science. 1991 Oct 25;254(5031):539–544. doi: 10.1126/science.1948029. [DOI] [PubMed] [Google Scholar]
  49. Pardi A., Billeter M., Wüthrich K. Calibration of the angular dependence of the amide proton-C alpha proton coupling constants, 3JHN alpha, in a globular protein. Use of 3JHN alpha for identification of helical secondary structure. J Mol Biol. 1984 Dec 15;180(3):741–751. doi: 10.1016/0022-2836(84)90035-4. [DOI] [PubMed] [Google Scholar]
  50. Piotto M., Saudek V., Sklenár V. Gradient-tailored excitation for single-quantum NMR spectroscopy of aqueous solutions. J Biomol NMR. 1992 Nov;2(6):661–665. doi: 10.1007/BF02192855. [DOI] [PubMed] [Google Scholar]
  51. Predki P. F., Agrawal V., Brünger A. T., Regan L. Amino-acid substitutions in a surface turn modulate protein stability. Nat Struct Biol. 1996 Jan;3(1):54–58. doi: 10.1038/nsb0196-54. [DOI] [PubMed] [Google Scholar]
  52. Pullman B., Pullman A. Molecular orbital calculations on the conformation of amino acid residues of proteins. Adv Protein Chem. 1974;28:347–526. doi: 10.1016/s0065-3233(08)60233-8. [DOI] [PubMed] [Google Scholar]
  53. Quinn T. P., Tweedy N. B., Williams R. W., Richardson J. S., Richardson D. C. Betadoublet: de novo design, synthesis, and characterization of a beta-sandwich protein. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8747–8751. doi: 10.1073/pnas.91.19.8747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Rance M., Sørensen O. W., Bodenhausen G., Wagner G., Ernst R. R., Wüthrich K. Improved spectral resolution in cosy 1H NMR spectra of proteins via double quantum filtering. Biochem Biophys Res Commun. 1983 Dec 16;117(2):479–485. doi: 10.1016/0006-291x(83)91225-1. [DOI] [PubMed] [Google Scholar]
  55. Richardson J. S. The anatomy and taxonomy of protein structure. Adv Protein Chem. 1981;34:167–339. doi: 10.1016/s0065-3233(08)60520-3. [DOI] [PubMed] [Google Scholar]
  56. Robertson D. E., Farid R. S., Moser C. C., Urbauer J. L., Mulholland S. E., Pidikiti R., Lear J. D., Wand A. J., DeGrado W. F., Dutton P. L. Design and synthesis of multi-haem proteins. Nature. 1994 Mar 31;368(6470):425–432. doi: 10.1038/368425a0. [DOI] [PubMed] [Google Scholar]
  57. Saxena V. P., Wetlaufer D. B. Formation of three-dimensional structure in proteins. I. Rapid nonenzymic reactivation of reduced lysozyme. Biochemistry. 1970 Dec 8;9(25):5015–5023. doi: 10.1021/bi00827a028. [DOI] [PubMed] [Google Scholar]
  58. Schafmeister C. E., LaPorte S. L., Miercke L. J., Stroud R. M. A designed four helix bundle protein with native-like structure. Nat Struct Biol. 1997 Dec;4(12):1039–1046. doi: 10.1038/nsb1297-1039. [DOI] [PubMed] [Google Scholar]
  59. Schafmeister C. E., Stroud R. M. Helical protein design. Curr Opin Biotechnol. 1998 Aug;9(4):350–353. doi: 10.1016/s0958-1669(98)80006-2. [DOI] [PubMed] [Google Scholar]
  60. Seo J., Cohen C. Pitch diversity in alpha-helical coiled coils. Proteins. 1993 Mar;15(3):223–234. doi: 10.1002/prot.340150302. [DOI] [PubMed] [Google Scholar]
  61. Soulier J., Madani A., Cacheux V., Rosenzwajg M., Sigaux F., Stern M. H. The MTCP-1/c6.1B gene encodes for a cytoplasmic 8 kD protein overexpressed in T cell leukemia bearing a t(X;14) translocation. Oncogene. 1994 Dec;9(12):3565–3570. [PubMed] [Google Scholar]
  62. Starovasnik M. A., Braisted A. C., Wells J. A. Structural mimicry of a native protein by a minimized binding domain. Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10080–10085. doi: 10.1073/pnas.94.19.10080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Stern M. H., Soulier J., Rosenzwajg M., Nakahara K., Canki-Klain N., Aurias A., Sigaux F., Kirsch I. R. MTCP-1: a novel gene on the human chromosome Xq28 translocated to the T cell receptor alpha/delta locus in mature T cell proliferations. Oncogene. 1993 Sep;8(9):2475–2483. [PubMed] [Google Scholar]
  64. Struthers M. D., Cheng R. P., Imperiali B. Design of a monomeric 23-residue polypeptide with defined tertiary structure. Science. 1996 Jan 19;271(5247):342–345. doi: 10.1126/science.271.5247.342. [DOI] [PubMed] [Google Scholar]
  65. Su J. Y., Hodges R. S., Kay C. M. Effect of chain length on the formation and stability of synthetic alpha-helical coiled coils. Biochemistry. 1994 Dec 27;33(51):15501–15510. doi: 10.1021/bi00255a032. [DOI] [PubMed] [Google Scholar]
  66. Wagner G., Braun W., Havel T. F., Schaumann T., Go N., Wüthrich K. Protein structures in solution by nuclear magnetic resonance and distance geometry. The polypeptide fold of the basic pancreatic trypsin inhibitor determined using two different algorithms, DISGEO and DISMAN. J Mol Biol. 1987 Aug 5;196(3):611–639. doi: 10.1016/0022-2836(87)90037-4. [DOI] [PubMed] [Google Scholar]
  67. Walsh S. T., Cheng H., Bryson J. W., Roder H., DeGrado W. F. Solution structure and dynamics of a de novo designed three-helix bundle protein. Proc Natl Acad Sci U S A. 1999 May 11;96(10):5486–5491. doi: 10.1073/pnas.96.10.5486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Wishart D. S., Sykes B. D., Richards F. M. The chemical shift index: a fast and simple method for the assignment of protein secondary structure through NMR spectroscopy. Biochemistry. 1992 Feb 18;31(6):1647–1651. doi: 10.1021/bi00121a010. [DOI] [PubMed] [Google Scholar]
  69. Wüthrich K., Billeter M., Braun W. Pseudo-structures for the 20 common amino acids for use in studies of protein conformations by measurements of intramolecular proton-proton distance constraints with nuclear magnetic resonance. J Mol Biol. 1983 Oct 5;169(4):949–961. doi: 10.1016/s0022-2836(83)80144-2. [DOI] [PubMed] [Google Scholar]
  70. Zhou N. E., Kay C. M., Hodges R. S. Synthetic model proteins. Positional effects of interchain hydrophobic interactions on stability of two-stranded alpha-helical coiled-coils. J Biol Chem. 1992 Feb 5;267(4):2664–2670. [PubMed] [Google Scholar]
  71. Zhou N. E., Kay C. M., Hodges R. S. Synthetic model proteins: the relative contribution of leucine residues at the nonequivalent positions of the 3-4 hydrophobic repeat to the stability of the two-stranded alpha-helical coiled-coil. Biochemistry. 1992 Jun 30;31(25):5739–5746. doi: 10.1021/bi00140a008. [DOI] [PubMed] [Google Scholar]
  72. Zhu B. Y., Zhou N. E., Kay C. M., Hodges R. S. Packing and hydrophobicity effects on protein folding and stability: effects of beta-branched amino acids, valine and isoleucine, on the formation and stability of two-stranded alpha-helical coiled coils/leucine zippers. Protein Sci. 1993 Mar;2(3):383–394. doi: 10.1002/pro.5560020310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. de Alba E., Santoro J., Rico M., Jiménez M. A. De novo design of a monomeric three-stranded antiparallel beta-sheet. Protein Sci. 1999 Apr;8(4):854–865. doi: 10.1110/ps.8.4.854. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES