Journal of Chemical Physics
Feedback | Help | Exit
The Journal of Chemical Physics
Search:
   
 
 
 
Previous Article
Size, shape, and flexibility of proteins and DNA
Size, shape, and flexibility are the important topological parameters which characterize the functional specificity and different types of interactions in proteins and DNA. The size of proteins and DN...
Next Article
Rheology and phase behavior of dense casein micelle dispersions
Casein micelle dispersions have been concentrated through osmotic stress and examined through rheological experiments. In conditions where the casein micelles are separated from each other, i.e., belo...

Dual folding pathways of an alpha/beta protein from all-atom ab initio folding simulations

J. Chem. Phys. 131, 165105 (2009); doi:10.1063/1.3238567

Published 29 October 2009

You are not logged in to this journal. Log in

Hongxing Lei,1,2 Zhi-Xiang Wang,2,3 Chun Wu,2 and Yong Duan2
1Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China
2Department of Applied Science and UC Davis Genome Center, One Shields Avenue, Davis, California 95616, USA
3Graduate School, Chinese Academy of Sciences, Beijing 100049, China
Successful ab initio folding of proteins with both alpha-helix and beta-sheet requires a delicate balance among a variety of forces in the simulation model, which may explain that the successful folding of any alpha/beta proteins to within experimental error has yet to be reported. Here we demonstrate that it is an achievable goal to fold alpha/beta proteins with a force field emphasizing the balance between the two major secondary structures. Using our newly developed force field, we conducted extensive ab initio folding simulations on an alpha/beta protein full sequence design (FSD) employing both conventional molecular dynamics and replica exchange molecular dynamics in combination with a generalized-Born solvation model. In these simulations, the folding of FSD to the native state with high population (>64.2%) and high fidelity (Calpha-Root Mean Square Deviation of 1.29 Å for the most sampled conformation when compared to the experimental structure) was achieved. The folding of FSD was found to follow two pathways. In the major pathway, the folding started from the formation of the helix. In the minor pathway, however, folding of the beta-hairpin started first. Further examination revealed that the helix initiated from the C-terminus and propagated toward the N-terminus. The formation of the hydrophobic contacts coincided with the global folding. Therefore the hydrophobic force does not appear to be the driving force of the folding of this protein. ©2009 American Institute of Physics
History: Received 4 March 2009; accepted 7 September 2009; published 29 October 2009
Permalink: http://link.aip.org/link/?JCPSA6/131/165105/1
BUY THIS ARTICLE   (US$24)
Download HTML Download Sectioned HTML Download PDF (1042 kB) View Cart

KEYWORDS and PACS

Keywords
PACS
  • 87.15.Cc
    Folding of biomolecules: thermodynamics, statistical mechanics, models and pathways
  • 87.15.hp
    Conformational changes of biomolecules
  • 36.20.Ey
    Macromolecular conformation (statistics and dynamics)
  • 87.14.E-
    Proteins
  • 87.15.ap
    Molecular dynamics simulation in molecular biophysics
  • 87.15.bd
    Secondary structure of biomolecules
  • YEAR: 2009

RELATED DATABASES


To view database links for this article,
you need to log in.
To view database links for this article,
you need to log in.

PUBLICATION DATA

ISSN:
0021-9606 (print)   1089-7690 (online)
Publisher:
AIP is a member of CrossRef AIP

REFERENCES (45)
View in Separate Window/Tab
For access to fully linked references, you need to log in. For access to fully linked references, you need to Log in.
  1. H. Hu, M. Elstner, and J. Hermans, Proteins 50, 451 (2003).
  2. T. Z. Lwin and R. Luo, Protein Sci. 15, 2642 (2006).
  3. A. Suenaga, T. Narumi, N. Futatsugi, R. Yanai, Y. Ohno, N. Okimoto, and M. Taiji, Asian J. Chem. 2, 591 (2007).
  4. W. X. Xu, T. F. Lai, Y. Yang, and Y. G. Mu, J. Chem. Phys. 128, 175105 (2008).
  5. T. Yoda, Y. Sugita, and Y. Okamoto, Proteins: Struct., Funct., Bioinf. 66, 846 (2007).
  6. S. Chowdhury, M. C. Lee, G. Xiong, and Y. Duan, J. Mol. Biol. 327, 711 (2003).
  7. J. W. Pitera and W. Swope, Proc. Natl. Acad. Sci. U.S.A. 100, 7587 (2003).
  8. C. D. Snow, B. Zagrovic, and V. S. Pande, J. Am. Chem. Soc. 124, 14548 (2002).
  9. H. Lei and Y. Duan, J. Mol. Biol. 370, 196 (2007).
  10. H. Lei, C. Wu, H. Liu, and Y. Duan, Proc. Natl. Acad. Sci. U.S.A. 104, 4925 (2007).
  11. D. R. Ripoll, J. A. Vila, and H. A. Scheraga, J. Mol. Biol. 339, 915 (2004).
  12. M. Y. Shen and K. F. Freed, Proteins 49, 439 (2002).
  13. H. Lei and Y. Duan, J. Phys. Chem. B 111, 5458 (2007).
  14. H. Lei, C. Wu, Z. X. Wang, Y. Zhou, and Y. Duan, J. Chem. Phys. 128, 235105 (2008).
  15. E. D. Nelson and N. V. Grishin, Proc. Natl. Acad. Sci. U.S.A. 105, 1489 (2008).
  16. S. Y. Kim, J. Lee, and J. Lee, Biophys. Chem. 115, 195 (2005).
  17. A. V. Rojas, A. Liwo, and H. A. Scheraga, J. Phys. Chem. B 111, 293 (2007).
  18. C. A. Sarisky and S. L. Mayo, J. Mol. Biol. 307, 1411 (2001).
  19. B. I. Dahiyat and S. L. Mayo, Science 278, 82 (1997).
  20. H. X. Lei and Y. Duan, J. Chem. Phys. 121, 12104 (2004).
  21. H. X. Lei, S. G. Dastidar, and Y. Duan, J. Phys. Chem. B 110, 22001 (2006).
  22. S. Jang, E. Kim, and Y. Pak, Proteins: Struct., Funct., Bioinf. 62, 663 (2006).
  23. S. Y. Kim, J. Lee, and J. Lee, J. Chem. Phys. 120, 8271 (2004).
  24. S. Mohanty and U. H. E. Hansmann, J. Chem. Phys. 127, 035102 (2007).
  25. W. F. Li, J. Zhang, and W. Wang, Proteins: Struct., Funct., Bioinf. 67, 338 (2007).
  26. D. A. Case, T. E. Cheatham, T. Darden, H. Gohlke, R. Luo, K. M. Merz, A. Onufriev, C. Simmerling, B. Wang, and R. J. Woods, J. Comput. Chem. 26, 1668 (2005).
  27. A. Onufriev, D. Bashford, and D. A. Case, Proteins 55, 383 (2004).
  28. U. H. E. Hansmann and Y. Okamoto, Phys. Rev. E 56, 2228 (1997).
  29. H. J. C. Berendsen, J. P. M. Postma, W. F. van Gunsteren, A. Dinola, and J. R. Haak, J. Chem. Phys. 81, 3684 (1984).
  30. J. P. Ryckaert, G. Ciccotti, and H. J. C. Berendsen, J. Comput. Phys. 23, 327 (1977).
  31. S. J. Weiner, P. A. Kollman, D. A. Case, U. C. Singh, C. Ghio, G. Alagona, S. Profeta, and P. Weiner, J. Am. Chem. Soc. 106, 765 (1984).
  32. W. D. Cornell, P. Cieplak, C. I. Bayly, I. R. Gould, K. M. Merz, D. M. Ferguson, D. C. Spellmeyer, T. Fox, J. W. Caldwell, and P. A. Kollman, J. Am. Chem. Soc. 117, 5179 (1995).
  33. C. I. Bayly, P. Cieplak, W. D. Cornell, and P. A. Kollman, J. Phys. Chem. 97, 10269 (1993).
  34. S. Miertus, E. Scrocco, and J. Tomasi, J. Chem. Phys. 55, 117 (1981).
  35. R. Cammi, B. Mennucci, and J. Tomasi, J. Phys. Chem. A 104, 5631 (2000).
  36. M. Cossi, G. Scalmani, N. Rega, and V. Barone, J. Chem. Phys. 117, 43 (2002).
  37. M. J. Frisch, G. W. Trucks, H. B. Schlegel et al., GAUSSIAN 03W, Revision B.04, Gaussian, Inc., Pittsburgh, PA, 2003.
  38. Y. Duan, C. Wu, S. Chowdhury, M. C. Lee, G. M. Xiong, W. Zhang, R. Yang, P. Cieplak, R. Luo, T. Lee, J. Caldwell, J. M. Wang, and P. Kollman, J. Comput. Chem. 24, 1999 (2003).
  39. A. D. MacKerell, M. Feig, and C. L. Brooks III, J. Am. Chem. Soc. 126, 698 (2004).
  40. J. H. Chen, W. P. Im, and C. L. Brooks III, J. Am. Chem. Soc. 128, 3728 (2006).
  41. A. D. MacKerell, D. Bashford, M. Bellott, R. L. Dunbrack, J. D. Evanseck, M. J. Field, S. Fischer, J. Gao, H. Guo, S. Ha, D. Joseph-McCarthy, L. Kuchnir, K. Kuczera, F. T. K. Lau, C. Mattos, S. Michnick, T. Ngo, D. T. Nguyen, B. Prodhom, W. E. Reiher, B. Roux, M. Schlenkrich, J. C. Smith, R. Stote, J. Straub, M. Watanabe, J. Wiorkiewicz-Kuczera, D. Yin, and M. Karplus, J. Phys. Chem. B 102, 3586 (1998).
  42. S. Jang, S. Shin, and Y. Pak, J. Am. Chem. Soc. 124, 4976 (2002).
  43. M. Karplus and D. L. Weaver, Protein Sci. 3, 650 (1994).
  44. S. A. Islam, M. Karplus, and D. L. Weaver, J. Mol. Biol. 318, 199 (2002).
  45. G. D. Rose, P. J. Fleming, J. R. Banavar, and A. Maritan, Proc. Natl. Acad. Sci. U.S.A. 103, 16623 (2006).

CITING ARTICLES
For access to citing articles, you need to log in.
For access to citing articles, you need to Log in.


Copyright © American Institute of Physics