Dynamics of Small, Folded Proteins

  • Petra Rovó
  • Dóra K. Menyhárd
  • Gábor Náray-Szabó
  • András PerczelEmail author


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.


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.


  1. 1.
    Bu Z, Callaway DJ (2011) Adv Protein Chem Struct Biol 83:163–221CrossRefGoogle Scholar
  2. 2.
    Zhao Q (2013) Rev Theor Sci 1:83–101CrossRefGoogle Scholar
  3. 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. 4.
    Namanja AT, Wang XJ, Xu B, Mercedes-Camacho AY, Wilson BD, Wilson KA, Etzkorn FA, Peng JW (2010) J Am Chem Soc 132:5607–5609CrossRefGoogle Scholar
  5. 5.
    Boehr DD, Nussinov R, Wright PE (2009) Nat Chem Biol 5:789–796CrossRefGoogle Scholar
  6. 6.
    Smock RG, Gierasch LM (2009) Science 324:198–203CrossRefGoogle Scholar
  7. 7.
    Kamerzell TJ, Middaugh CR (2008) Sending signals dynamically. J Pharm Sci 97:3494–3517CrossRefGoogle Scholar
  8. 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 35:539–546CrossRefGoogle Scholar
  9. 9.
    Khersonsky O, Tawfik DS (2010) Annu Rev Biochem 79:471–505CrossRefGoogle Scholar
  10. 10.
    Khoruzhii O, Butin O, Illarionov A, Leontyev I, Olevanov M, Ozrin V, Pereyaslavets L, Fain B, Chapter 5 of this bookGoogle Scholar
  11. 11.
    Wang W, Donini O, Reyes CM, Kollman PA (2001) Annu Rev Biophys 30:211–243CrossRefGoogle Scholar
  12. 12.
    Mackerell AD, Feig M, Brooks CL III (2004) J Comput Chem 25:1400–1415Google Scholar
  13. 13.
    Hu Z, Jiang J (2010) J Comput Chem 31:371–380CrossRefGoogle Scholar
  14. 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 26:1668–1688CrossRefGoogle Scholar
  15. 15.
  16. 16.
    Halgren TA (1996) J Comp Chem 17:490–519CrossRefGoogle Scholar
  17. 17.
    Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJ (2005) J Comput Chem 26:1701–1718CrossRefGoogle Scholar
  18. 18.
  19. 19.
  20. 20. Accessed 21 March 2014
  21. 21.
    Adcock SA, McCammon JA (2006) Chem Rev 106:1589–1615CrossRefGoogle Scholar
  22. 22.
    Allison JR, Hertig S, Missimer JH, Smith LJ, Steinmetz MO, Dolenc J (2012) J Chem Theory Comput 8:3430–3444CrossRefGoogle Scholar
  23. 23.
    Dror RO, Dirks RM, Grossman JP, Xu H, Shaw DE (2012) Annu Rev Biophys 41:429–452CrossRefGoogle Scholar
  24. 24.
    Genheden S, Ryde U (2012) Phys Chem Chem Phys 14:8662–8677CrossRefGoogle Scholar
  25. 25.
    Zhou R (2007) Methods Mol Biol 350:205–223Google Scholar
  26. 26.
    Sugita Y, Okamoto Y (1999) Chem Phys Lett 314:141–151CrossRefGoogle Scholar
  27. 27.
    Weber JK, Jack RL, Pande VS (2013) J Am Chem Soc 135:5501CrossRefGoogle Scholar
  28. 28.
    McGibbon R, Pande VS (2013) J Chem Theory Comput 9:2900–2906CrossRefGoogle Scholar
  29. 29.
    Tirion MM (1996) Phys Rev Lett 77:1905–1908CrossRefGoogle Scholar
  30. 30.
    Cui Q, Bahar I (2006) Normal mode analysis: theory and applications to biological and chemical systems. Chapman and Hall/CRC, Boca RatonGoogle Scholar
  31. 31.
    van den Bedem H, Bhabha G, Yang K, Wright PE, Fraser JS (2013) Nat Methods 10:896–902CrossRefGoogle Scholar
  32. 32.
    Staunton D, Schlinkert R, Zanetti G, Coelbrook SA, Campbell ID (2006) Magn Reson Chem 44:S2–S9CrossRefGoogle Scholar
  33. 33.
    Kainosho M, Torizawa T, Iwashita Y, Terauchi T, Ono AM (2006) Nature 440:52–57CrossRefGoogle Scholar
  34. 34.
    Gáspári Z, Pál G, Perczel A (2008) BioEssays 30:772–780CrossRefGoogle Scholar
  35. 35.
    Wüthrich K (1986) NMR of proteins and nucleic acids. WileyGoogle Scholar
  36. 36.
    Moseley HN, Monleon D, Montelione GT (2001) Methods Enzymol 339:91–108CrossRefGoogle Scholar
  37. 37.
    Jung YS, Zweckstetter M (2004) J Biomol NMR 30:11–23CrossRefGoogle Scholar
  38. 38.
    Hiller S, Wider G, Wüthrich K (2008) J Biomol NMR 42:179–195CrossRefGoogle Scholar
  39. 39.
    Fernandez C, Wider G (2003) Curr Opin Struct Biol 13:570–580CrossRefGoogle Scholar
  40. 40.
    Jarymowycz VA, Stone MJ (2006) Chem Rev 106:1624–1671CrossRefGoogle Scholar
  41. 41.
    Peng JW (2012) Phys Chem Lett 3:1039–1051CrossRefGoogle Scholar
  42. 42.
    Sapienza PJ, Lee AL (2010) Curr Opin Pharmacol 10:723–730CrossRefGoogle Scholar
  43. 43.
    Palmer AG (2001) Annu Rev Biophys Biomol Struct 30:129–155CrossRefGoogle Scholar
  44. 44.
    Igumenova TI, Frederick KK, Wand AJ (2006) Chem Rev 106:1672–1699CrossRefGoogle Scholar
  45. 45.
    Mittermaier AK, Kay LE (2009) Trends Biochem Sci 34:601–611CrossRefGoogle Scholar
  46. 46.
    Fischer MWF, Majumdar A, Zuiderweg ERP (1998) Prog Nucl Magn Reson Spectrosc 33:207–272CrossRefGoogle Scholar
  47. 47.
    Peng JW, Wagner GJ (1992) J Magn Reson 98:308–322Google Scholar
  48. 48.
    Peng JW, Wagner GJ (1992) Biochemistry 31:8571–8586CrossRefGoogle Scholar
  49. 49.
    Farrow NA, Zhang O, Forman-Kay JD, Kay LE (1995) Biochemistry 34:868–878CrossRefGoogle Scholar
  50. 50.
    Ishima R, Nagayama K (1995) J Magn Reson Ser B 108:73–76CrossRefGoogle Scholar
  51. 51.
    Redfield AG (2012) J Biomol NMR 52:159–177CrossRefGoogle Scholar
  52. 52.
    Lipari G, Szabo A (1982) J Am Chem Soc 104(4546–4559):4559–4570CrossRefGoogle Scholar
  53. 53.
    Palmer AG (1997) Curr Opin Struct Biol 7:732–737CrossRefGoogle Scholar
  54. 54.
    Carr HY, Purcell EM (1954) Phys Rev 94:630–638CrossRefGoogle Scholar
  55. 55.
    Meiboom S, Gill D (1958) Rev Sci Instrum 29:688–691CrossRefGoogle Scholar
  56. 56.
    Peng JW, Thanabal V, Wagner G (1991) J Magn Reson 94:82–100Google Scholar
  57. 57.
    Mulder FAA, de Graaf RA, Kaptein R, Boelens R (1998) J Magn Reson 131:351–357CrossRefGoogle Scholar
  58. 58.
    Palmer AG III, Massi F (2006) Chem Rev 106:1700–1719CrossRefGoogle Scholar
  59. 59.
    Jeener J, Meier BH, Bachmann P, Ernst RR (1979) J Chem Phys 71:4546–4553CrossRefGoogle Scholar
  60. 60.
    Neidigh JW, Fesinmeyer RM, Andersen NH (2002) Nat Struct Biol 9:425–430CrossRefGoogle Scholar
  61. 61.
    Barua B, Lin JC, Williams VD, Kummler P, Neidigh JW, Andersen NH (2008) Protein Eng Des Sel 21:171–185CrossRefGoogle Scholar
  62. 62.
    Williams DV, Barua B, Andersen NH (2008) Org Biomol Chem 6:4287–4289CrossRefGoogle Scholar
  63. 63.
    Williams DV, Byrne A, Stewart J, Andersen NH (2011) Biochemistry 50:1143–1152CrossRefGoogle Scholar
  64. 64.
    Neidigh JW, Fesinmeyer RM, Prickett KS, Andersen NH (2001) Biochemistry 40:13188–13200CrossRefGoogle Scholar
  65. 65.
    Neuweiler H, Doose S, Sauer M (2005) Proc Natl Acad Sci USA 102:16650–16655CrossRefGoogle Scholar
  66. 66.
    Ahmed Z, Beta IA, Mikhonin AV, Asher SA (2005) J Am Chem Soc 127:10943–10950CrossRefGoogle Scholar
  67. 67.
    Mok KH, Kuhn LT, Goez M, Day IJ, Lin JC, Andersen NH, Hore PJ (2007) Nature 447:106–109CrossRefGoogle Scholar
  68. 68.
    Culik RM, Serrano AL, Bunagan MR, Gai F (2011) Angew Chem Int Ed Engl 50:10884–10887CrossRefGoogle Scholar
  69. 69.
    Qiu L, Pabit SA, Roitberg AE, Hagen SJ (2002) J Am Chem Soc 124:12952–12953CrossRefGoogle Scholar
  70. 70.
    Mok KH, Kuhn LT, Goez M, Day IJ, Lin JC, Andersen NH, Hore PJ (2007) Nature 447:106–109CrossRefGoogle Scholar
  71. 71.
    Neuweiler H, Doose S, Sauer M (2005) Proc Natl Acad Sci USA 102:16650–16655CrossRefGoogle Scholar
  72. 72.
    Rovó P, Stráner P, Láng A, Bartha I, Huszár K, Nyitray L, Perczel A (2013) Chem Eur J 19:2628–2640CrossRefGoogle Scholar
  73. 73.
    Juraszek J, Bolhuis PG (2008) Biophys J 95:4246–4257CrossRefGoogle Scholar
  74. 74.
    Juraszek J, Bolhuis PG (2006) Proc Natl Acad Sci USA 103:15859–15864CrossRefGoogle Scholar
  75. 75.
    Chowdhury S, Lee MC, Xiong G, Duan Y (2003) J Mol Biol 327:711–717CrossRefGoogle Scholar
  76. 76.
    Zheng W, Gallicchio E, Deng N, Andrec M, Levy RM (2011) J Phys Chem B 115:1512–1523CrossRefGoogle Scholar
  77. 77.
    Zhou R (2003) Proc Natl Acad Sci USA 100:13280–13285CrossRefGoogle Scholar
  78. 78.
    Linhananta J, Boer I, MacKay J (2005) J Chem Phys 122:114901CrossRefGoogle Scholar
  79. 79.
    Nikiforovich GV, Andersen NH, Fesinmeyer RM, Frieden C (2003) Proteins: Struct Funct Bioinf 52:292–302CrossRefGoogle Scholar
  80. 80.
    Snow CD, Zagrovic B, Pande VS (2002) J Am Chem Soc 124:14548–14549CrossRefGoogle Scholar
  81. 81.
    Paschek D, Nymeyer H, Garcia AE (2007) J Struct Biol 157:524–533CrossRefGoogle Scholar
  82. 82.
    Paschek D, Hempel S, García AE (2008) Proc Natl Acad Sci USA 105:17754–17759CrossRefGoogle Scholar
  83. 83.
    Zagrovic B, Pande V (2003) J Comput Chem 24:1432–1436CrossRefGoogle Scholar
  84. 84.
    Day R, Paschek D, Garcia AE (2010) Proteins: Struct Funct Bioinf 78:1889–1899Google Scholar
  85. 85.
    Dyer RB (2007) Curr Opin Struct Biol 17:38–47CrossRefGoogle Scholar
  86. 86.
    Rodriguez-Granillo A, Annavarapu S, Zhang L, Koder RV, Nanda V (2011) J Am Chem Soc 133:18750–18759CrossRefGoogle Scholar
  87. 87.
    Mackerell AD Jr, Feig M, Brooks CL III (2004) J Comput Chem 25:1400–1415CrossRefGoogle Scholar
  88. 88.
    Lindorff-Larsen K, Piana S, Palmo K, Maragakis P, Klepeis JL, Dror RO, Shaw DE (2010) Proteins 78:1950–1958Google Scholar
  89. 89.
    Kaminski GA, Friesner RA, Tirado-Rives J, Jorgensen WL (2001) J Phys Chem B 105:6474–6487CrossRefGoogle Scholar
  90. 90.
    Hess B, Kutzner C, van der Spoel D, Lindahl E (2008) J Chem Theory Comput 4:435–447CrossRefGoogle Scholar
  91. 91.
    Lindorff-Larsen K, Maragakis P, Piana S, Eastwood MP, Dror RO, Shaw DE (2012) PLoS ONE 7(2):e32131CrossRefGoogle Scholar
  92. 92.
    Scian M, Lin JC, Trong IL, Makhatadze GI, Stenkamp RE, Andersen NH (2012) Proc Natl Acad Sci USA 109:12521–12525CrossRefGoogle Scholar
  93. 93.
    Marinelli F, Pietrucci F, Laio A, Piana S (2009) PLoS Comput Biol. doi: 10.1371/journal.pcbi.1000452 Google Scholar
  94. 94.
    Jimenez-Cruz CA, Makhatadze GI, Garcia AE (2011) Phys Chem Chem Phys 13:17056–17063CrossRefGoogle Scholar
  95. 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. 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 46:299–304CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Petra Rovó
    • 1
  • Dóra K. Menyhárd
    • 2
  • Gábor Náray-Szabó
    • 1
  • András Perczel
    • 1
    • 2
    Email author
  1. 1.Laboratory of Structural Chemistry and Biology, Institute of ChemistryEötvös Loránd UniversityBudapestHungary
  2. 2.MTA-ELTE Protein Modelling Research GroupBudapestHungary

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