Skip to main content

Dynamics of Small, Folded Proteins

  • 1245 Accesses

Abstract

Beyond static properties, like primary sequence, folding, electrostatics, etc. protein action is also influenced by dynamic factors, which may essentially influence structure and function. In this chapter first we give a short outline of various methods for the computer modelling of protein dynamics, then discuss the most important experimental technique, nuclear magnetic resonance spectroscopy applied to proteins. Combined application of these two methods will be illustrated on two small proteins, extensively studied in our laboratory. First we discuss the Trp-cage protein, to our knowledge the smallest one with essential attributes of basic protein properties. Our second case study deals with podocin, an interesting small protein. Its dynamic properties determine potential malfunction, the inheritance of a specific kidney disease.

Keywords

  • Nuclear Magnetic Resonance
  • Relaxation Rate
  • Nuclear Magnetic Resonance Spectroscopy
  • Nuclear Magnetic Resonance Experiment
  • Folding Process

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-3-319-09976-7_10
  • Chapter length: 26 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   99.00
Price excludes VAT (USA)
  • ISBN: 978-3-319-09976-7
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   129.99
Price excludes VAT (USA)
Hardcover Book
USD   159.99
Price excludes VAT (USA)
Fig. 10.1
Fig. 10.2
Fig. 10.3
Fig. 10.4
Fig. 10.5
Fig. 10.6
Fig. 10.7
Fig. 10.8
Fig. 10.9
Fig. 10.10
Fig. 10.11

References

  1. Bu Z, Callaway DJ (2011) Adv Protein Chem Struct Biol 83:163–221

    CrossRef  CAS  Google Scholar 

  2. Zhao Q (2013) Rev Theor Sci 1:83–101

    CrossRef  Google Scholar 

  3. Baker CM, Best RB (2013) Insights into the binding of intrinsically disordered proteins from molecular dynamics simulation. WIREs Comput Mol Sci. doi:10.1002/wcms.1167

    Google Scholar 

  4. Namanja AT, Wang XJ, Xu B, Mercedes-Camacho AY, Wilson BD, Wilson KA, Etzkorn FA, Peng JW (2010) J Am Chem Soc 132:5607–5609

    CrossRef  CAS  Google Scholar 

  5. Boehr DD, Nussinov R, Wright PE (2009) Nat Chem Biol 5:789–796

    CrossRef  CAS  Google Scholar 

  6. Smock RG, Gierasch LM (2009) Science 324:198–203

    CrossRef  CAS  Google Scholar 

  7. Kamerzell TJ, Middaugh CR (2008) Sending signals dynamically. J Pharm Sci 97:3494–3517

    CrossRef  CAS  Google Scholar 

  8. Csermely P, Palotai R, Nussinov R (2010) Induced fit, conformational selection and independent dynamic segments: an extended view of binding events. Trends Biochem Sci 35:539–546

    CrossRef  CAS  Google Scholar 

  9. Khersonsky O, Tawfik DS (2010) Annu Rev Biochem 79:471–505

    CrossRef  CAS  Google Scholar 

  10. Khoruzhii O, Butin O, Illarionov A, Leontyev I, Olevanov M, Ozrin V, Pereyaslavets L, Fain B, Chapter 5 of this book

    Google Scholar 

  11. Wang W, Donini O, Reyes CM, Kollman PA (2001) Annu Rev Biophys 30:211–243

    CrossRef  CAS  Google Scholar 

  12. Mackerell AD, Feig M, Brooks CL III (2004) J Comput Chem 25:1400–1415

    Google Scholar 

  13. Hu Z, Jiang J (2010) J Comput Chem 31:371–380

    CrossRef  CAS  Google Scholar 

  14. Case DA, Cheatham TE III, Darden T, Gohlke H, Luo R, Merz KM Jr, Onufriev A, Simmerling C, Wang B, Woods RJ (2005) J Comput Chem 26:1668–1688

    CrossRef  CAS  Google Scholar 

  15. http://www.gromacs.org/Documentation/Terminology/Force_Fields/GROMOS. Accessed 21 March 2014

  16. Halgren TA (1996) J Comp Chem 17:490–519

    CrossRef  CAS  Google Scholar 

  17. Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJ (2005) J Comput Chem 26:1701–1718

    CrossRef  Google Scholar 

  18. http://accelrys.com/products/discovery-studio/. Accessed 21 March 2014

  19. https://www.certara.com/products/molmod/sybyl-x. Accessed 21 March 2014

  20. http://www.charmm.org/. Accessed 21 March 2014

  21. Adcock SA, McCammon JA (2006) Chem Rev 106:1589–1615

    CrossRef  CAS  Google Scholar 

  22. Allison JR, Hertig S, Missimer JH, Smith LJ, Steinmetz MO, Dolenc J (2012) J Chem Theory Comput 8:3430–3444

    CrossRef  CAS  Google Scholar 

  23. Dror RO, Dirks RM, Grossman JP, Xu H, Shaw DE (2012) Annu Rev Biophys 41:429–452

    CrossRef  CAS  Google Scholar 

  24. Genheden S, Ryde U (2012) Phys Chem Chem Phys 14:8662–8677

    CrossRef  CAS  Google Scholar 

  25. Zhou R (2007) Methods Mol Biol 350:205–223

    CAS  Google Scholar 

  26. Sugita Y, Okamoto Y (1999) Chem Phys Lett 314:141–151

    CrossRef  CAS  Google Scholar 

  27. Weber JK, Jack RL, Pande VS (2013) J Am Chem Soc 135:5501

    CrossRef  CAS  Google Scholar 

  28. McGibbon R, Pande VS (2013) J Chem Theory Comput 9:2900–2906

    CrossRef  CAS  Google Scholar 

  29. Tirion MM (1996) Phys Rev Lett 77:1905–1908

    CrossRef  CAS  Google Scholar 

  30. Cui Q, Bahar I (2006) Normal mode analysis: theory and applications to biological and chemical systems. Chapman and Hall/CRC, Boca Raton

    Google Scholar 

  31. van den Bedem H, Bhabha G, Yang K, Wright PE, Fraser JS (2013) Nat Methods 10:896–902

    CrossRef  Google Scholar 

  32. Staunton D, Schlinkert R, Zanetti G, Coelbrook SA, Campbell ID (2006) Magn Reson Chem 44:S2–S9

    CrossRef  CAS  Google Scholar 

  33. Kainosho M, Torizawa T, Iwashita Y, Terauchi T, Ono AM (2006) Nature 440:52–57

    CrossRef  CAS  Google Scholar 

  34. Gáspári Z, Pál G, Perczel A (2008) BioEssays 30:772–780

    CrossRef  Google Scholar 

  35. Wüthrich K (1986) NMR of proteins and nucleic acids. Wiley

    Google Scholar 

  36. Moseley HN, Monleon D, Montelione GT (2001) Methods Enzymol 339:91–108

    CrossRef  CAS  Google Scholar 

  37. Jung YS, Zweckstetter M (2004) J Biomol NMR 30:11–23

    CrossRef  CAS  Google Scholar 

  38. Hiller S, Wider G, Wüthrich K (2008) J Biomol NMR 42:179–195

    CrossRef  CAS  Google Scholar 

  39. Fernandez C, Wider G (2003) Curr Opin Struct Biol 13:570–580

    CrossRef  CAS  Google Scholar 

  40. Jarymowycz VA, Stone MJ (2006) Chem Rev 106:1624–1671

    CrossRef  CAS  Google Scholar 

  41. Peng JW (2012) Phys Chem Lett 3:1039–1051

    CrossRef  CAS  Google Scholar 

  42. Sapienza PJ, Lee AL (2010) Curr Opin Pharmacol 10:723–730

    CrossRef  CAS  Google Scholar 

  43. Palmer AG (2001) Annu Rev Biophys Biomol Struct 30:129–155

    CrossRef  CAS  Google Scholar 

  44. Igumenova TI, Frederick KK, Wand AJ (2006) Chem Rev 106:1672–1699

    CrossRef  CAS  Google Scholar 

  45. Mittermaier AK, Kay LE (2009) Trends Biochem Sci 34:601–611

    CrossRef  CAS  Google Scholar 

  46. Fischer MWF, Majumdar A, Zuiderweg ERP (1998) Prog Nucl Magn Reson Spectrosc 33:207–272

    CrossRef  CAS  Google Scholar 

  47. Peng JW, Wagner GJ (1992) J Magn Reson 98:308–322

    CAS  Google Scholar 

  48. Peng JW, Wagner GJ (1992) Biochemistry 31:8571–8586

    CrossRef  CAS  Google Scholar 

  49. Farrow NA, Zhang O, Forman-Kay JD, Kay LE (1995) Biochemistry 34:868–878

    CrossRef  CAS  Google Scholar 

  50. Ishima R, Nagayama K (1995) J Magn Reson Ser B 108:73–76

    CrossRef  CAS  Google Scholar 

  51. Redfield AG (2012) J Biomol NMR 52:159–177

    CrossRef  CAS  Google Scholar 

  52. Lipari G, Szabo A (1982) J Am Chem Soc 104(4546–4559):4559–4570

    CrossRef  CAS  Google Scholar 

  53. Palmer AG (1997) Curr Opin Struct Biol 7:732–737

    CrossRef  CAS  Google Scholar 

  54. Carr HY, Purcell EM (1954) Phys Rev 94:630–638

    CrossRef  CAS  Google Scholar 

  55. Meiboom S, Gill D (1958) Rev Sci Instrum 29:688–691

    CrossRef  CAS  Google Scholar 

  56. Peng JW, Thanabal V, Wagner G (1991) J Magn Reson 94:82–100

    CAS  Google Scholar 

  57. Mulder FAA, de Graaf RA, Kaptein R, Boelens R (1998) J Magn Reson 131:351–357

    CrossRef  CAS  Google Scholar 

  58. Palmer AG III, Massi F (2006) Chem Rev 106:1700–1719

    CrossRef  CAS  Google Scholar 

  59. Jeener J, Meier BH, Bachmann P, Ernst RR (1979) J Chem Phys 71:4546–4553

    CrossRef  CAS  Google Scholar 

  60. Neidigh JW, Fesinmeyer RM, Andersen NH (2002) Nat Struct Biol 9:425–430

    CrossRef  CAS  Google Scholar 

  61. Barua B, Lin JC, Williams VD, Kummler P, Neidigh JW, Andersen NH (2008) Protein Eng Des Sel 21:171–185

    CrossRef  CAS  Google Scholar 

  62. Williams DV, Barua B, Andersen NH (2008) Org Biomol Chem 6:4287–4289

    CrossRef  CAS  Google Scholar 

  63. Williams DV, Byrne A, Stewart J, Andersen NH (2011) Biochemistry 50:1143–1152

    CrossRef  CAS  Google Scholar 

  64. Neidigh JW, Fesinmeyer RM, Prickett KS, Andersen NH (2001) Biochemistry 40:13188–13200

    CrossRef  CAS  Google Scholar 

  65. Neuweiler H, Doose S, Sauer M (2005) Proc Natl Acad Sci USA 102:16650–16655

    CrossRef  CAS  Google Scholar 

  66. Ahmed Z, Beta IA, Mikhonin AV, Asher SA (2005) J Am Chem Soc 127:10943–10950

    CrossRef  CAS  Google Scholar 

  67. Mok KH, Kuhn LT, Goez M, Day IJ, Lin JC, Andersen NH, Hore PJ (2007) Nature 447:106–109

    CrossRef  CAS  Google Scholar 

  68. Culik RM, Serrano AL, Bunagan MR, Gai F (2011) Angew Chem Int Ed Engl 50:10884–10887

    CrossRef  CAS  Google Scholar 

  69. Qiu L, Pabit SA, Roitberg AE, Hagen SJ (2002) J Am Chem Soc 124:12952–12953

    CrossRef  CAS  Google Scholar 

  70. Mok KH, Kuhn LT, Goez M, Day IJ, Lin JC, Andersen NH, Hore PJ (2007) Nature 447:106–109

    CrossRef  CAS  Google Scholar 

  71. Neuweiler H, Doose S, Sauer M (2005) Proc Natl Acad Sci USA 102:16650–16655

    CrossRef  CAS  Google Scholar 

  72. Rovó P, Stráner P, Láng A, Bartha I, Huszár K, Nyitray L, Perczel A (2013) Chem Eur J 19:2628–2640

    CrossRef  Google Scholar 

  73. Juraszek J, Bolhuis PG (2008) Biophys J 95:4246–4257

    CrossRef  CAS  Google Scholar 

  74. Juraszek J, Bolhuis PG (2006) Proc Natl Acad Sci USA 103:15859–15864

    CrossRef  CAS  Google Scholar 

  75. Chowdhury S, Lee MC, Xiong G, Duan Y (2003) J Mol Biol 327:711–717

    CrossRef  CAS  Google Scholar 

  76. Zheng W, Gallicchio E, Deng N, Andrec M, Levy RM (2011) J Phys Chem B 115:1512–1523

    CrossRef  CAS  Google Scholar 

  77. Zhou R (2003) Proc Natl Acad Sci USA 100:13280–13285

    CrossRef  CAS  Google Scholar 

  78. Linhananta J, Boer I, MacKay J (2005) J Chem Phys 122:114901

    CrossRef  Google Scholar 

  79. Nikiforovich GV, Andersen NH, Fesinmeyer RM, Frieden C (2003) Proteins: Struct Funct Bioinf 52:292–302

    CrossRef  CAS  Google Scholar 

  80. Snow CD, Zagrovic B, Pande VS (2002) J Am Chem Soc 124:14548–14549

    CrossRef  CAS  Google Scholar 

  81. Paschek D, Nymeyer H, Garcia AE (2007) J Struct Biol 157:524–533

    CrossRef  CAS  Google Scholar 

  82. Paschek D, Hempel S, García AE (2008) Proc Natl Acad Sci USA 105:17754–17759

    CrossRef  CAS  Google Scholar 

  83. Zagrovic B, Pande V (2003) J Comput Chem 24:1432–1436

    CrossRef  CAS  Google Scholar 

  84. Day R, Paschek D, Garcia AE (2010) Proteins: Struct Funct Bioinf 78:1889–1899

    CAS  Google Scholar 

  85. Dyer RB (2007) Curr Opin Struct Biol 17:38–47

    CrossRef  CAS  Google Scholar 

  86. Rodriguez-Granillo A, Annavarapu S, Zhang L, Koder RV, Nanda V (2011) J Am Chem Soc 133:18750–18759

    CrossRef  CAS  Google Scholar 

  87. Mackerell AD Jr, Feig M, Brooks CL III (2004) J Comput Chem 25:1400–1415

    CrossRef  CAS  Google Scholar 

  88. Lindorff-Larsen K, Piana S, Palmo K, Maragakis P, Klepeis JL, Dror RO, Shaw DE (2010) Proteins 78:1950–1958

    CAS  Google Scholar 

  89. Kaminski GA, Friesner RA, Tirado-Rives J, Jorgensen WL (2001) J Phys Chem B 105:6474–6487

    CrossRef  CAS  Google Scholar 

  90. Hess B, Kutzner C, van der Spoel D, Lindahl E (2008) J Chem Theory Comput 4:435–447

    CrossRef  CAS  Google Scholar 

  91. Lindorff-Larsen K, Maragakis P, Piana S, Eastwood MP, Dror RO, Shaw DE (2012) PLoS ONE 7(2):e32131

    CrossRef  CAS  Google Scholar 

  92. Scian M, Lin JC, Trong IL, Makhatadze GI, Stenkamp RE, Andersen NH (2012) Proc Natl Acad Sci USA 109:12521–12525

    CrossRef  CAS  Google Scholar 

  93. Marinelli F, Pietrucci F, Laio A, Piana S (2009) PLoS Comput Biol. doi:10.1371/journal.pcbi.1000452

    Google Scholar 

  94. Jimenez-Cruz CA, Makhatadze GI, Garcia AE (2011) Phys Chem Chem Phys 13:17056–17063

    CrossRef  CAS  Google Scholar 

  95. Rogne P, Ozdowy P, Richter C, Saxena K, Schwalbe H, Kuhn LT (2012) PLoS ONE. doi:10.1371/journal.pone.0041301

    Google Scholar 

  96. Tory K, Menyhárd DK, Woerner S, Nevo F, Gribouval O, Kerti A, Stráner P, Arrondel C, Cong EH, Tulassay T, Mollet G, Perczel A, Antignac C (2014) Nat Genet 46:299–304

    CrossRef  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to András Perczel .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Rovó, P., Menyhárd, D.K., Náray-Szabó, G., Perczel, A. (2014). Dynamics of Small, Folded Proteins. In: Náray-Szabó, G. (eds) Protein Modelling. Springer, Cham. https://doi.org/10.1007/978-3-319-09976-7_10

Download citation