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All-Atom Monte Carlo Simulations of Protein Folding and Aggregation

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Computational Methods to Study the Structure and Dynamics of Biomolecules and Biomolecular Processes

Part of the book series: Springer Series in Bio-/Neuroinformatics ((SSBN,volume 1))

Abstract

The ability to aggregate into β-sheet-rich fibrillar structures is a common property shared by many proteins. However, the propensity to aggregate and the precise mechanisms involved vary from protein to protein. Two currently intensely studied proteins are the Alzheimer’s-related amyloid β-peptide (Aβ) and the Parkinson’s-related α-synuclein (αS), both of which are disordered as free monomers and form fibrils. Here, we present studies of Aβ monomers and dimers and monomeric αS, based on an implicit solvent all-atom Monte Carlo (MC) approach. Somewhat unexpectedly, in the αS study, two distinct phases are observed. As a result, in the simulations, disordered αS has to overcome a rather large free-energy barrier in order to acquire a fibril-like fold. No corresponding barrier is observed in the Aβ simulations. Recently, the same computational model was used to study the folding of the Top7 protein, with > 90 residues and a mixed α + β fold. This chapter provides a summary of these Aβ , αS and Top7 studies.

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References

  1. Chiti, F., Dobson, C.M.: Annu. Rev. Biochem. 75, 333 (2006)

    Article  Google Scholar 

  2. Knowles, T.P.J., Shu, W., Devlin, G.L., Meehan, S., Auer, S., Dobson, C.M., Welland, M.E.: Proc. Natl. Acad. Sci. USA 104, 10016 (2007)

    Article  Google Scholar 

  3. Wu, C., Shea, J.E.: Curr. Opin. Struct. Biol. 21, 209 (2011)

    Article  Google Scholar 

  4. Pellarin, R., Guarnera, E., Caflisch, A.: J. Mol. Biol. 374, 917 (2007)

    Article  Google Scholar 

  5. Zhang, J., Muthukumar, M.: J. Chem. Phys. 130, 035102 (2009)

    Article  Google Scholar 

  6. Auer, S., Kashchiev, D.: Phys. Rev. Lett. 104, 168105 (2010)

    Article  Google Scholar 

  7. Straub, J.E., Thirumalai, D.: Curr. Opin. Struct. Biol. 20, 187 (2010)

    Article  Google Scholar 

  8. Lindorff-Larsen, K., Piana, S., Dror, R., Shaw, D.: Science 334, 517 (2011)

    Article  Google Scholar 

  9. Sgourakis, N.G., Yan, Y., McCallum, S.A., Wang, C., García, A.E.: J. Mol. Biol. 368, 1448 (2007)

    Article  Google Scholar 

  10. Olubiyi, O.O., Strödel, B.: J. Phys. Chem. B 116, 3280 (2012)

    Article  Google Scholar 

  11. Mitternacht, S., Staneva, I., Härd, T., Irbäck, A.: Proteins 78, 2600 (2010)

    Google Scholar 

  12. Mitternacht, S., Staneva, I., Härd, T., Irbäck, A.: Mol. J. Mol. Biol. 410, 357 (2011)

    Article  Google Scholar 

  13. Jónsson, S.Æ., Mohanty, S., Irbäck, A.: Proteins 80, 2169 (2012)

    Google Scholar 

  14. Mohanty, S., Meinke, J., Zimmermann, O.: Proteins (2013), doi:10.1002/prot.24295

    Google Scholar 

  15. Irbäck, A., Mitternacht, S., Mohanty, S.: PMC Biophys. 2, 2 (2009)

    Article  Google Scholar 

  16. Mitsutake, A., Sugita, Y., Okamoto, Y.: Biopolymers 60, 96 (2001)

    Article  Google Scholar 

  17. Shirvanyants, D., Ding, F., Tsao, D., Ramanchandran, S., Dokholyan, N.V.: J. Phys. Chem. B 116, 8375 (2012)

    Google Scholar 

  18. Bartels, T., Choi, J.G., Selkoe, D.J.: Nature 477, 107 (2011)

    Article  Google Scholar 

  19. Kuhlman, B., Dantas, G., Ireton, G.C., Varani, G., Stoddard, B.L., Baker, D.: Science 302, 1364 (2003)

    Article  Google Scholar 

  20. Luheshi, L.M., Tartaglia, G.G., Brorsson, A., Pawar, A.P., Watson, I.E., Chiti, F., Vendruscolo, M., Lomas, D.A., Dobson, C.M., Crowther, D.C.: PLoS Biol. 5, e290 (2007)

    Article  Google Scholar 

  21. Brorsson, A.C., Bolognesi, B., Tartaglia, G.G., Shammas, S.L., Favrin, G., Watson, I., Lomas, D.A., Chiti, F., Vendruscolo, M., Dobson, C.M., Crowther, D.C., Luheshi, L.M.: Biophys. J. 98, 1677 (2010)

    Article  Google Scholar 

  22. Irbäck, A., Mohanty, S.: J. Comput. Chem. 27, 1548 (2006)

    Article  Google Scholar 

  23. Irbäck, A., Samuelsson, B., Sjunnesson, F., Wallin, S.: Biophys. J. 85, 1466 (2003)

    Article  Google Scholar 

  24. Cheon, M., Chang, I., Mohanty, S., Luheshi, L.M., Dobson, C.M., Vendruscolo, M., Favrin, G.: PLoS Comput. Biol. 3, e173 (2007)

    Article  Google Scholar 

  25. Irbäck, A., Mitternacht, S.: Proteins 71, 207 (2008)

    Article  Google Scholar 

  26. Li, D., Mohanty, S., Irbäck, A., Huo, S.: PLoS Comput. Biol. 4, e1000238 (2008)

    Article  Google Scholar 

  27. Irbäck, A., Mitternacht, S., Mohanty, S.: Proc. Natl. Acad. Sci. USA 102, 13427 (2005)

    Article  Google Scholar 

  28. Mitternacht, S., Luccioli, S., Torcini, A., Imparato, A., Irbäck, A.: Biophys. J. 96, 429 (2009)

    Article  Google Scholar 

  29. Bachmann, M., Goede, K., Beck-Sickinger, A., Grundmann, M., Irbäck, A., Janke, W.: Angew. Chem. Int. Edit. 49, 9530 (2010)

    Article  Google Scholar 

  30. Favrin, G., Irbäck, A., Sjunnesson, F.: J. Chem. Phys. 114, 8154 (2001)

    Article  Google Scholar 

  31. Madras, N., Sokal, A.D.: J. Stat. Phys. 50, 109 (1988)

    Article  MathSciNet  MATH  Google Scholar 

  32. Dodd, L.R., Boone, T.D., Theodorou, D.N.: Molec. Phys. 78, 961 (1993)

    Article  Google Scholar 

  33. Bottaro, S., Boomsma, W., Johansson, K.E., Andreetta, C., Hamelryck, T., Ferkinghoff-Borg, J.: J. Chem. Theory Comput. 8, 695 (2012)

    Article  Google Scholar 

  34. Ulmschneider, J.P., Jorgensen, W.L.: J. Chem. Phys. 118, 4261 (2003)

    Article  Google Scholar 

  35. Swendsen, R.H., Wang, J.S.: Phys. Rev. Lett. 57, 2607 (1986)

    Article  MathSciNet  Google Scholar 

  36. Marinari, E., Parisi, G.: Europhys. Lett. 19, 451 (1992)

    Article  Google Scholar 

  37. Lyubartsev, A.P., Martsinovski, A.A., Shevkunov, S.V., Vorontsov-Velyaminov, P.N.: J. Chem. Phys. 96, 1776 (1992)

    Article  Google Scholar 

  38. Jónsson, S.Æ., Mohanty, S., Irbäck, A.: J. Chem. Phys. 135, 125102 (2011)

    Article  Google Scholar 

  39. Wang, F., Landau, D.P.: Phys. Rev. Lett. 86, 2050 (2001)

    Article  Google Scholar 

  40. Berg, B.A., Neuhaus, T.: Phys. Lett. B 267, 249 (1991)

    Article  Google Scholar 

  41. Ferrenberg, A.M., Swendsen, R.H.: Phys. Rev. Lett. 63, 1195 (1989)

    Article  Google Scholar 

  42. Anand, P., Nandel, F.S., Hansmann, U.H.E.: J. Chem. Phys. 129, 195102 (2008)

    Article  Google Scholar 

  43. Barz, B., Urbanc, B.: PLoS One 7, e34345 (2011)

    Article  Google Scholar 

  44. Côté, S., Laghaei, R., Derreumaux, P., Mousseau, N.: J. Phys. Chem. B 116, 4043 (2012)

    Article  Google Scholar 

  45. Chong, S.H., Ham, S.: Phys. Chem. Chem. Phys. 14, 1573 (2012)

    Article  Google Scholar 

  46. Laganowsky, A., Liu, C., Sawaya, M.R., Whitelegge, J.P., Park, J., Zhao, M., Pensalfini, A., Soriaga, A.B., Landau, M., Teng, P.K., Cascio, D., Glabe, C., Eisenberg, D.: Science 335, 1228 (2012)

    Article  Google Scholar 

  47. Stroud, J.C., Liu, C., Teng, P.K., Eisenberg, D.: Proc. Natl. Acad. Sci. USA 109, 7717 (2012)

    Article  Google Scholar 

  48. Petkova, A.T., Ishii, Y., Balbach, J.J., Antzutkin, O.N., Leapman, R.D., Delaglio, F., Tycko, R.: Proc. Natl. Acad. Sci. USA 99, 16742 (2002)

    Article  Google Scholar 

  49. Lührs, T., Ritter, C., Adrian, M., Riek-Loher, D., Bohrmann, B., Döbeli, H., Schubert, D., Riek, R.: Proc. Natl. Acad. Sci. USA 102, 17342 (2005)

    Article  Google Scholar 

  50. Sciarretta, K.L., Gordon, D.J., Petkova, A.T., Tycko, R., Meredith, S.C.: Biochemistry 44, 6003 (2005)

    Article  Google Scholar 

  51. Grant, M.A., Lazo, N.D., Lomakin, A., Condron, M.M., Arai, H., Yamin, G., Rigby, A.C., Teplow, D.B.: Proc. Natl. Acad. Sci. USA 104, 16522 (2007)

    Article  Google Scholar 

  52. Sandal, M., Valle, F., Tessari, I., Mammi, S., Bergantino, E., Musiani, F., Brucale, M., Bubacco, L., Samorì, B.: PLoS Biol. 6, e6 (2008)

    Article  Google Scholar 

  53. Frimpong, A.K., Abzalimov, R.R., Uversky, V.N., Kaltashov, I.A.: Proteins 78, 714 (2010)

    Google Scholar 

  54. Dedmon, M.M., Lindorff-Larsen, K., Christodoulou, J., Vendruscolo, M., Dobson, C.M.: J. Am. Chem. Soc. 127, 476 (2005)

    Article  Google Scholar 

  55. Allison, J.R., Varnai, P., Dobson, C.M., Vendruscolo, M.: J. Am. Chem. Soc. 131, 18314 (2009)

    Article  Google Scholar 

  56. Wu, K.P., Weinstock, D.S., Narayanan, C., Levy, R.M., Baum, J.: J. Mol. Biol. 391, 784 (2009)

    Article  Google Scholar 

  57. Wu, K.P., Kim, S., Fela, D.A., Baum, J.: J. Mol. Biol. 378, 1104 (2008)

    Article  Google Scholar 

  58. Kim, H.Y., Heise, H., Fernandez, C.O., Baldus, M., Zweckstetter, M.: ChemBioChem. 8, 1671 (2007)

    Article  MATH  Google Scholar 

  59. Vilar, M., Chou, H.T., Lührs, T., Maji, S.K., Riek-Loher, D., Verel, R., Manning, G., Stahlberg, H., Riek, R.: Proc. Natl. Acad. Sci. USA 105, 8637 (2008)

    Article  Google Scholar 

  60. DeLano, W.L.: The PyMOL molecular graphics system. DeLano Scientific, San Carlos (2002)

    Google Scholar 

  61. Hellstrand, E., Boland, B., Walsh, D.M., Linse, S.: ACS Chem. Neurosci. 1, 13 (2010)

    Article  Google Scholar 

  62. Grey, M., Linse, S., Nilsson, H., Brundin, P., Sparr, E.: J. Parkinson’s Dis. 1, 359 (2011)

    Google Scholar 

  63. Levitan, K., Chereau, D., Cohen, S.I.A., Knowles, T.P.J., Dobson, C.M., Fink, A.L., Anderson, J.P., Goldstein, J.M., Millhauser, G.L.: J. Mol. Biol. 411, 329 (2011)

    Article  Google Scholar 

  64. Ahmad, B., Chen, Y., Lapidus, L.J.: Proc. Natl. Acad. Sci. USA 109, 2336 (2012)

    Article  Google Scholar 

  65. Watters, A.L., Deka, P., Corrent, C., Callender, D., Varani, G., Sosnick, T., Baker, D.: Cell 128, 613 (2007)

    Article  Google Scholar 

  66. Mohanty, S., Meinke, J.H., Zimmermann, O., Hansmann, U.H.E.: Proc. Natl. Acad. Sci. USA 105, 8004 (2008)

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Astronomy and Theoretical Physics, Lund University, Sölvegatan 14A, SE-223 62, Lund, Sweden

    Anders Irbäck

  2. Institute for Advanced Simulation, Jülich Supercomputing Centre, Forschungszentrum Jülich, D-52425, Jülich, Germany

    Sandipan Mohanty

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  1. Anders Irbäck
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  2. Sandipan Mohanty
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Correspondence to Anders Irbäck .

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Editors and Affiliations

  1. , Faculty of Chemistry, University of Gdansk, Sobieskiego 18, Gdansk, 80-952, Poland

    Adam Liwo

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Irbäck, A., Mohanty, S. (2014). All-Atom Monte Carlo Simulations of Protein Folding and Aggregation. In: Liwo, A. (eds) Computational Methods to Study the Structure and Dynamics of Biomolecules and Biomolecular Processes. Springer Series in Bio-/Neuroinformatics, vol 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28554-7_13

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  • DOI: https://doi.org/10.1007/978-3-642-28554-7_13

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-28553-0

  • Online ISBN: 978-3-642-28554-7

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