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JCP: BioChemical Physics / Volume 6 / Issue 9 / ARTICLES

J. Chem. Phys. 137, 105103 (2012); http://dx.doi.org/10.1063/1.4752247 (7 pages)

Lattice model simulations of the effects of the position of a peptide trigger segment on helix folding and dimerization

Yuba R. Bhandari, Prem P. Chapagain, and Bernard S. Gerstman

Department of Physics, Florida International University, University Park, Miami, Florida 33199, USA

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(Received 18 June 2012; accepted 29 August 2012; published online 13 September 2012)

The folding and dimerization of proteins is greatly facilitated by the presence of a trigger site, a segment of amino acids that has a higher propensity for forming α-helix structure as compared to the rest of the chain. In addition to the helical propensity of each chain, dimerization can also be facilitated by interhelical interactions such as saltbridges, and interfacial contacts of different strengths. In this work, we are interested in understanding the interplay of these interactions in a model peptide system. We investigate how these different interactions influence the kinetics of dimer formation and the stability of the fully formed dimer. We use lattice model computer simulations to investigate how the effectiveness of the trigger segment and its saltbridges depends on the location along the protein primary sequence. For different positions of the trigger segment, heat capacity and free energy of unfolded and folded configurations are calculated to study the thermodynamics of folding and dimerization. The kinetics of the process is investigated by calculating characteristic folding times. The thermodynamic and kinetic data from the simulations combine to show that the dimerization process of the model system is faster when the segment with high helical propensity is located near either end of the peptide, as compared to the middle of the chain. The dependence of the stability of the dimer on the trigger segment's position is also studied. The stability can play a role in the ability of the dimer to perform a biological function that involves partial unzipping. The results on folding and dimer stability provide important insights for designing proteins that involve trigger sites.

© 2012 American Institute of Physics

Article Outline

  1. INTRODUCTION
  2. MATERIALS AND METHODS
    1. Computer lattice model
    2. Dimer model and the positions of the trigger site
  3. RESULTS AND DISCUSSION
    1. Dimerization timescales
    2. Unfolding timescales and dimer stability
    3. Free energy and heat capacity calculations
  4. CONCLUSIONS

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KEYWORDS, PACS, and IPC

Keywords

association, biochemistry, free energy, molecular biophysics, molecular configurations, proteins, specific heat

PACS

International Patent Classification (IPC)

  • C12

    Biochemistry; Beer; Spirits; Wine; Vinegar; Microbiology; Enzymology; Mutation or genetic engineering

ARTICLE DATA

Digital Object Identifier
http://dx.doi.org/10.1063/1.4752247

PUBLICATION DATA

ISSN

1931-9223 (online)

Publisher

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

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    References

    P. P. Chapagain, Y. Liu, and B. S. Gerstman, J. Chem. Phys. 129(17), 175103 (2008)JCPSA6000129000017175103000001.

    Y. Liu, P. P. Chapagain, J. L. Parra, and B. S. Gerstman, J. Chem. Phys. 128(4), 045106 (2008)JCPSA6000128000004045106000001.

    B. S. Gerstman and P. P. Chapagain, J. Chem. Phys. 123(5), 054901 (2005)JCPSA6000123000005054901000001.

    P. P. Chapagain, J. L. Parra, B. S. Gerstman, and Y. Liu, J. Chem. Phys. 127(7), 075103 (2007)JCPSA6000127000007075103000001.

    A. M. Ferrenberg and R. H. Swendsen, Phys. Rev. Lett. 63(12), 1195 (1989).

    N. D. Socci and J. N. Onuchic, J. Chem. Phys. 103(11), 4732 (1995)JCPSA6000103000011004732000001.


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