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Journal of Chemical Physics / Volume 134 / Issue 22 / ARTICLES / Biological Molecules, Biopolymers, and Biological Systems
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J. Chem. Phys. 134, 225101 (2011); http://dx.doi.org/10.1063/1.3592712 (11 pages)

Simulations of the confinement of ubiquitin in self-assembled reverse micelles

Jianhui Tian and Angel E. García

Department of Physics, Applied Physics and Astronomy and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, USA

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(Received 21 March 2011; accepted 30 April 2011; published online 8 June 2011)

We describe the effects of confinement on the structure, hydration, and the internal dynamics of ubiquitin encapsulated in reverse micelles (RM). We performed molecular dynamics simulations of the encapsulation of ubiquitin into self-assembled protein/surfactant reverse micelles to study the positioning and interactions of the protein with the RM and found that ubiquitin binds to the RM interface at low salt concentrations. The same hydrophobic patch that is recognized by ubiquitin binding domains  in vivo is found to make direct contact with the surfactant head groups, hydrophobic tails, and the iso-octane solvent. The fast backbone N-H relaxation dynamics show that the fluctuations of the protein encapsulated in the RM are reduced when compared to the protein in bulk. This reduction in fluctuations can be explained by the direct interactions of ubiquitin with the surfactant and by the reduced hydration environment within the RM. At high concentrations of excess salt, the protein does not bind strongly to the RM interface and the fast backbone dynamics are similar to that of the protein in bulk. Our simulations demonstrate that the confinement of protein can result in altered protein dynamics due to the interactions between the protein and the surfactant.

© 2011 American Institute of Physics

Article Outline

  1. INTRODUCTION
  2. METHODS
    1. Simulations of ubiquitin-AOT RM Self assembly
    2. Simulations of ubiquitin in bulk water
    3. Simulations of ubiquitin in pre-assembled RM
    4. Simulations of ubiquitin in pre-assembled neutral surfactant RM
    5. Potential of mean force calculations of ubiquitin positioning in RM
    6. Analysis of trajectories
  3. RESULTS AND DISCUSSION
    1. Self-assembly process and ubiquitin encapsulation
    2. Backbone N-H relaxation
    3. Backbone hydration structure
    4. Protein internal hydration
    5. Interactions of ubiquitin with AOTs
    6. Location of ubiquitin within RM
    7. Potential of mean force calculations
  4. CONCLUSIONS

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KEYWORDS and PACS

Keywords

biochemistry, encapsulation, fluctuations, hydrophobicity, molecular biophysics, molecular dynamics method, proteins, self-assembly, solvation

PACS

ARTICLE DATA

Digital Object Identifier
http://dx.doi.org/10.1063/1.3592712

PUBLICATION DATA

ISSN

0021-9606 (print)  
1089-7690 (online)

Publisher

$abstract.society.value is a Member of CrossRef American Institute of Physics

  1. R. Ellis and A. Minton, Nature (London) 425, 27 (2003). [ISI] [MEDLINE] [CAS]
  2. H.-X. Zhou, G. Rivas, and A. P. Minton, Ann. Rev. Biophys. 37, 375 (2008).
  3. H. Zhou and K. Dill, Biochem. J. 40, 11289 (2001). [ISI] [MEDLINE] [CAS]
  4. M. Cheung, D. Klimov, and D. Thirumalai, Proc. Natl. Acad. Sci. U.S.A. 102, 4753 (2005). [MEDLINE]
  5. L. M. Charlton, C. O. Barnes, C. Li, J. Orans, G. B. Young, and G. J. Pielak, J. Am. Chem. Soc. 130, 6826 (2008).
  6. A. Verkman, Trends Biol. Sci. 27, 27 (2002).
  7. R. Peterson, K. Anbalagan, C. Tommos, and A. Wand, J. Am. Chem. Soc. 126, 9498 (2004). [MEDLINE] [CAS]
  8. D. Homouz, M. Perham, A. Samiotakis, M. S. Cheung, and P. Wittung-Stafshede, Proc. Natl. Acad. Sci. U.S.A. 105, 11754 (2008). [MEDLINE]
  9. A. Kudlay, M. S. Cheung, and D. Thirumalai, Phys. Rev. Lett. 102 (2009).
  10. L. Stagg, S.-Q. Zhang, M. S. Cheung, and P. Wittung-Stafshede, Proc. Natl. Acad. Sci. U.S.A. 104, 18976 (2007). [MEDLINE]
  11. A. Massari, I. Finkelstein, and M. Fayer, J. Am. Chem. Soc. 128, 3990 (2006).
  12. D. D.L. Minh, C.-E. Chang, J. Trylska, V. Tozzini, and J. A. McCammon, J. Am. Chem. Soc. 128, 6006 (2006). [MEDLINE] [CAS]
  13. L. Ellerby, C. Nishida, F. Nishida, S. Yamanaka, B. Dunn, J. Valentine, and J. Zink, Science 255, 1113 (1992). [MEDLINE]
  14. S. Mukherjee, P. Chowdhury, and F. Gai, J. Phys. Chem. B 113, 531 (2009).
  15. D. Eggers and J. Valentine, Protein. Sci. 10, 250 (2001). [ISI] [MEDLINE]
  16. W. D. Van Horn, M. E. Ogilvie, and P. F. Flynn, J. Am. Chem. Soc. 131, 8030 (2009).
  17. S. Mukherjee, P. Chowdhury, W. F. DeGrado, and F. Gai, Langmuir 23, 11174 (2007). [MEDLINE]
  18. R. Peterson, M. Pometun, Z. Shi, and A. Wand, Protein Sci. 14, 2919 (2005).
  19. C. Joazeiro and T. Hunter, Science 289, 2061 (2000).
  20. P. Maragakis, K. Lindorff-Larsen, M. P. Eastwood, R. O. Dror, J. L. Klepeis, I. T. Arkin, M. O. Jensen, H. Xu, N. Trbovic, R. A. Friesner, A. G. Palmer, and D. E. Shaw, J. Phys. Chem. B 112, 6155 (2008). [Inspec]
  21. A. Nederveen and A. Bonvin, J. Chem. Theory Comput. 1, 363 (2005). [CAS]
  22. N. Tjandra, S. Feller, R. Pastor, and A. Bax, J. Am. Chem. Soc. 117, 12562 (1995). [ISI] [CAS]
  23. S. Lienin, T. Bremi, B. Brutscher, R. Bruschweiler, and R. Ernst, J. Am. Chem. Soc. 120, 9870 (1998). [ISI] [CAS]
  24. A. Wand, M. Ehrhardt, and P. Flynn, Proc. Natl. Acad. Sci. U.S.A. 95, 15299 (1998). [ISI] [MEDLINE]
  25. C. Babu, P. Flynn, and A. Wand, J. Am. Chem. Soc. 123, 2691 (2001).
  26. J. Tian and A. E. Garcia, Biophys. J. 96, L57 (2009).
  27. V. S. Chaitanya and S. Senapati, J. Am. Chem. Soc. 130, 1866 (2008). [MEDLINE] [CAS]
  28. J. Henin and C. Chipot, J. Chem. Phys. 121, 2904 (2004)JCPSA6000121000007002904000001. [ISI] [MEDLINE]
  29. S. Abel, F. Sterpone, S. Bandyopadhyay, and M. Marchi, J. Phys. Chem. B 108, 19458 (2004).
  30. V. Hornak, R. Abel, A. Okur, B. Strockbine, A. Roitberg, and C. Simmerling, Proteins: Struct., Funct., Bioinf. 65, 712 (2006). [MEDLINE]
  31. M. Martin and J. Siepmann, J. Phys. Chem. B 103, 4508 (1999). [ISI] [CAS]
  32. S. Abel, M. Waks, and M. Marchi, Eur. Phys. J. E 32, 399 (2010).
  33. A. V. Martinez, S. C. DeSensi, L. Dominguez, E. Rivera, and J. E. Straub, J. Chem. Phys. 134, 055107 (2011)JCPSA6000134000005055107000001. [MEDLINE]
  34. J. Phillips, R. Braun, W. Wang, J. Gumbart, E. Tajkhorshid, E. Villa, C. Chipot, R. Skeel, L. Kale, and K. Schulten, J. Comput. Chem. 26, 1781 (2005). [MEDLINE]
  35. S. Feller, Y. Zhang, R. Pastor, and B. Brooks, J. Chem. Phys. 103, 4613 (1995).
  36. G. J. Martyna, M. L. Klein, and M. Tuckerman, J. Chem. Phys. 97, 2635 (1992)JCPSA6000097000004002635000001.
  37. T. A. Darden, D. York, and L. Pedersen, J. Chem. Phys. 98, 10089 (1993).
  38. J. P. Ryckaert, G. Ciccotti, and H. J.C. Berendsen, J. Comput. Phys. 23, 327 (1977).
  39. S. Miyamoto and P. A. Kollman, J. Comput. Chem. 13, 952 (1992).
  40. See supplementary material at http://dx.doi.org/10.1063/1.3592712 providing further details about protein fluctuations, diffusion of ubiquitin inside the RM and partial charges for the neutral AOT headgroups. [EPAPS]
  41. J. Prompers and R. Bruschweiler, J. Am. Chem. Soc. 124, 4522 (2002). [MEDLINE] [CAS]
  42. G. Lipari and A. Szabo, J. Am. Chem. Soc. 104, 4546 (1982). [Inspec] [ISI] [CAS]
  43. G. Lipari and A. Szabo, J. Am. Chem. Soc. 104, 4559 (1982). [Inspec] [ISI]
  44. A. Palmer, Chem. Rev. 104, 3623 (2004). [ISI] [MEDLINE]
  45. A. E. Garcia and G. Hummer, Proteins: Struct., Funct., Genet. 38, 261 (2000).
  46. A. E. Garcia and L. Stiller, J. Comput. Chem. 14, 1396 (1993).
  47. R. Day and A. E. Garcia, Proteins: Struct., Funct., Genet. 70, 1175 (2008).
  48. N. G. Sgourakis, R. Day, S. A. McCallum, and A. E. Garcia, Biophys. J. 95, 3943 (2008).
  49. G. Hummer and A. Szabo, J. Chem. Phys. 105, 2004 (1996)JCPSA6000105000005002004000001. [ISI] [CAS]
  50. P. M. Petrone and A. E. Garcia, J. Mol. Bio. 338, 419 (2004). [MEDLINE] [CAS]
  51. W. Humphrey, A. Dalke, and K. Schulten, J. Mol. Graphics 14, 33 (1996). [MEDLINE]
  52. A. K. Simorellis and P. F. Flynn, J. Am. Chem. Soc. 128, 9580 (2006).
  53. A. Simorellis, W. Van Horn, and P. Flynn, J. Am. Chem. Soc. 128, 5082 (2006). [MEDLINE] [CAS]
  54. S. A. Showalter and R. Bruschweiler, J. Chem. Theor. Comput. 3, 961 (2007).
  55. M. A. Williams, J. M. Goodfellow, and J. M. Thornton, Protein Sci. 3, 1224 (1994). [MEDLINE]
  56. S. Park and J. Saven, Proteins: Struct., Funct., Bioinf. 60, 450 (2005).
  57. M. Davidovic, C. Mattea, J. Qvist, and B. Halle, J. Am. Chem. Soc. 131, 1025 (2009).
  58. A. Damjanovic, B. Garcia-Moreno, E. Lattman, and A. E. Garcia, Proteins: Struct., Funct,. Bioinf. 60, 433 (2005).
  59. V. Denisov and B. Halle, J. Mol. Bio. 245, 682 (1995). [ISI] [MEDLINE]
  60. E. Persson and B. Halle, J. Am. Chem. Soc. 130, 1774 (2008). [MEDLINE] [CAS]
  61. K. Naoe, K. Noda, M. Kawagoe, and M. Imai, Colloids Surf., B 38, 179 (2004);, Symposium on Colloid and Soft Matters, Yokohama, JAPAN, OCT 11-13, 2003.
  62. C. Petit, P. Brochette, and M. P. Pileni, J. Phys. Chem. 90, 6517 (1986). [ISI]
  63. E. Melo, P. Fojan, J. Cabral, and S. Petersen, Chem. Phys. Lipids 106, 181 (2000). [MEDLINE]
  64. O. F. Lange, N.-A. Lakomek, C. Fares, G. F. Schroeder, K. F.A. Walter, S. Becker, J. Meiler, H. Grubmueller, C. Griesinger, and B. L. de Groot, Science 320, 1471 (2008). [MEDLINE]
  65. L. Hicke, H. Schubert, and C. Hill, Nat. Rev. Mol. Cell Bio. 6, 610 (2005).
  66. C. Babu, V. Hilser, and A. Wand, Nat. Struct. Mol. Bio. 11, 352 (2004). [MEDLINE] [CAS]
  67. M. S. Pometun, R. W. Peterson, C. R. Babu, and A. J. Wand, J. Am. Chem. Soc. 128, 10652 (2006).
  68. W. Van Horn, A. Simorellis, and P. Flynn, J. Am. Chem. Soc. 127, 13553 (2005). [MEDLINE] [CAS]
  69. K. M. Larsson and M. P. Pileni, Eur. Biophys. J. 21, 409 (1993). [ISI] [CAS]
  70. J. Pinero, L. Bhuiyan, and D. Bratko, J. Chem. Phys. 120, 11941 (2004)JCPSA6000120000024011941000001. [ISI]
  71. A. M. Dokter, S. Woutersen, and H. J. Bakker, Proc. Natl. Acad. Sci. U.S.A. 103, 15355 (2006). [MEDLINE]
  72. D. E. Moilanen, N. E. Levinger, D. B. Spry, and M. D. Fayer, J. Am. Chem. Soc. 129, 14311 (2007). [MEDLINE]
  73. E. E. Fenn, D. B. Wong, and M. D. Fayer, Proc. Natl. Acad. Sci. U.S.A. 106, 15243 (2009).

Figures (click on thumbnails to view enlargements)

FIG.1
Structure of a RM containing ubiquitin. (a) Position of the protein (in CPK) inside a self-assembled RM. (b) Exterior surface view of the RM. Water molecules are shown as a red surface, AOT molecules are shown as a gray surface, Na ions are shown as orange spheres. The protein is shown in a CPK model. Ubiquitin binds to the AOT surfactants through the hydrophobic patch formed by residues Leu 8, Ile 44, and Val 70(green). This hydrophobic patch is surrounded by positively charged residues Lys 6, Lys 11, Arg 42, Lys 48, His 68, Arg 72, and Arg 74 (white). (c) Interior view of the ubiquitin/AOT interface. The protein is shown in a ribbon model, except for sidechains that interact directly with AOT molecules. The N- (Met 1) and C- (Gly 76) termini amino acids are labeled. The figure was prepared using the VMD (Ref. 51).

FIG.1 Download High Resolution Image (.zip file) | Export Figure to PowerPoint

FIG.2
LS model free S2 Order parameters calculated using iRED, SiRED2, and internal correlation function, S Ct 2, for URM compared with experimental data, S exp 2. The black circle is from Simorellis and Flynns NMR experiments, the upper part red triangles are S2 calculated from iRED using 10 ns blocks and the blue triangles are S2 calculated using internal correlation function, and the low parts are the corresponding difference between simulation and experimental data. The inset shows a scatter plot of the experimental and simulation order parameters. The dashed line represents y = x curve, with intercept zero and slope 1.

FIG.2 Download High Resolution Image (.zip file) | Export Figure to PowerPoint

FIG.3
Comparison of LS model free S2 order parameters for ubiquitin in URM and in UBK. The black line corresponds to the order parameters in UBK, S UBK 2, and the red line corresponds to the order parameters in URM, SURM2. The blue line corresponds to the difference between URM and UBK with positive values denoting larger order parameters in URM.

FIG.3 Download High Resolution Image (.zip file) | Export Figure to PowerPoint

FIG.4
Comparison of Eigenmode collectivity in URM and UBK systems. The red circles are the eigenvalues and the corresponding collectivity of the eigenmode in URM, while the black squares are those in UBK. κ is a measure of the relative number of N-H vectors that are significantly affected by a given mode (Ref. 41).

FIG.4 Download High Resolution Image (.zip file) | Export Figure to PowerPoint

FIG.5
Comparison of N-H water coordination number and S2. Black line shows N-H water coordination number difference for URM and UBK systems; red line shows N-H order parameter difference in URM and UBK systems.

FIG.5 Download High Resolution Image (.zip file) | Export Figure to PowerPoint

FIG.6
Water Pockets in Ubiquitin: on the left is water pocket-U, which is located at the loop region of residues 18 to 22. Water molecules in this pocket form hydrogen bonds with the Glu 18 and Asp 21 carbonyl oxygens. On the right is water pocket V, which is located between beta-sheet III and beta-sheet IV. Water molecules in this pocket form hydrogen bonds with the Leu 43 nitrogen and the Leu 50 carbonyl oxygen.

FIG.6 Download High Resolution Image (.zip file) | Export Figure to PowerPoint

FIG.7
(a) Coordination number of ubiquitin side chains to surfactant heavy atoms. (b) Ubiquitin tertiary structure with residues that have large AOT heavy atoms coordination shown in red.

FIG.7 Download High Resolution Image (.zip file) | Export Figure to PowerPoint

FIG.8
Potential of mean force for ubiquitin in a RM with (a) low excess salt concentration (0.187 M NaCl), (b) at higher excess salt concentration (1 M NaCl) , and (c) in an idealized neutral head group surfactants. The reaction coordinate is the distance between center of mass of ubiquitin and center of mass of the RM.

FIG.8 Download High Resolution Image (.zip file) | Export Figure to PowerPoint

Supplemental Files (EPAPS)

Tables

Table I. Final Composition of self-assembled RMs that contains an ubiquitin molecule.

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Table II. Number of penetrating and solvating waters for ubiquitin in URM and UBK environments.

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Table III. Excess chemical potential for waters in pocket-U.

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