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Journal of Chemical Physics / Volume 135 / Issue 23 / ARTICLES / Biological Molecules, Biopolymers, and Biological Systems

J. Chem. Phys. 135, 235104 (2011); http://dx.doi.org/10.1063/1.3668288 (10 pages)

Structure change of β-hairpin induced by turn optimization: An enhanced sampling molecular dynamics simulation study

Qiang Shao, Lijiang Yang, and Yi Qin Gao

College of Chemistry and Molecular Engineering, Beijing National Laboratory for Molecular Sciences, Peking University, Beijing 100871, China

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(Received 6 September 2011; accepted 21 November 2011; published online 20 December 2011)

Our previous study showed that for the tested polypeptides which have similar β-hairpin structures but different sequences, their folding free energy pathways are dominantly determined by the turn conformational propensity. In this study, we study how the turn conformational propensity affects the structure of hairpins. The folding of two mutants of GB1p peptide (GB1m2 and GB1m3), which have the optimized turn sequence (6DDATK11T → 6NPATG11K) with native structures unsolved, were simulated using integrated tempering sampling molecular dynamics simulations and the predicted stable structures were compared to wild-type GB1p. It was observed that the turn optimization of GB1p generates a more favored 5-residue type I′ turn in addition to the 6-residue type I turn in wild-type GB1p. As a result two distinctly different hairpin structures are formed corresponding to the “misfolded” (M) and the “folded” (F) states. M state is a one-residue-shifted asymmetric β-hairpin structure whereas F state has the similar symmetric hairpin structure as wild-type GB1p. The formation of the favored type I′ turn has a small free energy barrier and leads to the shifted β-hairpin structure, following the modified “zipping” model. The presence of disfavored type I turn structure makes the folding of a β-hairpin consistent with the “hydrophobic-core-centric” model. On the other hand, the folding simulations on other two GB1p mutants (GB1r1 and GBr2), which have the position of the hydrophobic core cluster further away from the turn compared to wild-type GB1p, showed that moving the hydrophobic core cluster away from the turn region destabilizes but does not change the hairpin structure. Therefore, the present study showed that the turn conformational propensity is a key factor in affecting not only the folding pathways but also the stable structure of β-hairpins, and the turn conformational change induced by the turn optimization leads to significant changes of β-hairpin structure.

© 2011 American Institute of Physics

Article Outline

  1. INTRODUCTION
  2. MATERIALS AND METHODS
  3. RESULTS
    1. Further validation of the force field
    2. Hairpin structures of the mutants of GB1p peptide
    3. Folding free energy landscape analysis of the mutants of GB1p peptide
    4. The stability of hydrogen bonds
  4. DISCUSSION AND CONCLUSIONS

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KEYWORDS and PACS

Keywords

biological techniques, free energy, molecular biophysics, molecular configurations, molecular dynamics method, proteins

PACS

ARTICLE DATA

Digital Object Identifier
http://dx.doi.org/10.1063/1.3668288

PUBLICATION DATA

ISSN

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

Publisher

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

For access to fully linked references, you need to log in.
    Q. Shao, L. J. Yang, and Y. Q. Gao, J. Chem. Phys. 130, 195104 (2009)JCPSA6000130000019195104000001.


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