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TRAJELIX: A Computational Tool for the Geometric Characterization of Protein Helices During Molecular Dynamics Simulations

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Summary

We have developed a computer program with the necessary mathematical formalism for the geometric characterization of distorted conformations of alpha-helices proteins, such as those that can potentially be sampled during typical molecular dynamics simulations. This formalism has been incorporated into TRAJELIX, a new module within the SIMULAID framework (http://inka.mssm.edu/~mezei/simulaid/) that is capable of monitoring distortions of alpha-helices in terms of their displacement, global and local tilting, rotation around their axes, compression/extension, winding/unwinding, and bending. Accurate evaluation of these global and local structural properties of the helix can help study possible intramolecular and intermolecular changes in the helix packing of alpha-helical membrane proteins, as shown here in an application to the interacting helical domains of rhodopsin dimers. Quantification of the dynamic structural behavior of alpha-helical membrane proteins is critical for our understanding of signal transduction, and may enable structure-based design of more specific and efficient drugs.

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References

  1. Sansom M.S., Weinstein H., 2000, Trends. Pharmacol. Sci. 21: 445

    Article  CAS  Google Scholar 

  2. Barlow D.J., Thornton J.M., 1988, J. Mol. Biol. 201: 601

    Article  CAS  Google Scholar 

  3. Kumar S., Bansal M., 1998, Biophys. J. 75: 1935

    Article  CAS  Google Scholar 

  4. Christopher J.A., Swanson R., Baldwin T.O., 1996, Computer Chemistry 20: 339

    Article  CAS  Google Scholar 

  5. Mezei, M., Simulaid: simulation setup utilities http://inka. mssm/edu/∼ ∼mezei/simulaid

  6. Bansal M., Kumar S., Velavan R., 2000, J. Biomol. Struct. Dyn. 17: 811

    CAS  Google Scholar 

  7. van der Spoel, D., van Druner, R. and Berendsen, H.J.C., GROningen MAchine for Chemical Simulation. Department of Biophysical Chemistry. BIOSON Research Institute, Groningen, The Netherlands

  8. Liang Y., Fotiadis D., Filipek S., Saperstein D.A., Palczewski K., Engel A., 2003, J Biol. Chem. 278: 21655

    Article  CAS  Google Scholar 

  9. Lazaridis T., 2003, Proteins 52: 176

    Article  CAS  Google Scholar 

  10. Kabsch W., Sander C., 1983, Biopolymers 22: 2577

    Article  CAS  Google Scholar 

  11. Rose G.D., Seltzer J.P., 1977, J. Mol. Biol. 113: 153

    Article  CAS  Google Scholar 

  12. Kahn P.C., 1989, Computers and Chemistry 13: 191

    Article  Google Scholar 

  13. Wani, J.K., Probability and Statistical Inference; Appelton-Century-Crofts 1971

  14. Westbrook J.D., Fitzgerald P.M., 2003, Methods Biochem. Anal. 44: 161

    CAS  Google Scholar 

  15. Brooks B.R., Bruccoleri R.E., Olafson B.D., States D.J., Swaminathan S., Karplus M., 1983, J. Comp. Chem. 4: 187

    Article  CAS  Google Scholar 

  16. Weiner P.K., Kollman P.A., 1981, J. Comp. Chem. 2: 287

    Article  CAS  Google Scholar 

  17. Mohamadi F., Richards N.G.J., Guida W.C., Liskamp R., Lipton M., Caufield C., Chang G., Hendrickson T., Still W.C., 1990, J. Comp. Chem. 11: 440

    Article  CAS  Google Scholar 

  18. Accelrys, InsightII; http://www.accelrys.com/insight/index. html

  19. Mezei, M., MMC: Monte Carlo program for simulation of molecular assemblies; http://inka.mssm.edu/∼ ∼mezei/mmc

  20. Kale L., Skeel R., Bhandarkar M., Brunner R., Gursoy A., Krawetz N., Phillips J., Shinozaki A., Varadarajan K., Schulten K., 1999, J. Comput. Phys. 151: 283

    Article  CAS  Google Scholar 

  21. Ravishanker G., Swaminathan S., Beveridge D.L., Lavery R., Sklenar H., 1989, J. Biomol. Struct. Dyn. 6: 669

    CAS  Google Scholar 

  22. Bai M., 2004, Cell Signal 16: 175

    Article  CAS  Google Scholar 

  23. Javitch J.A., 2004, Mol. Pharmacol. 66: 1077

    Article  CAS  Google Scholar 

  24. Liebmann C., 2004, Curr. Pharm. Des. 10: 1937

    Article  CAS  Google Scholar 

  25. Milligan G., 2004, Mol. Pharmacol. 66: 1

    Article  CAS  Google Scholar 

  26. Park P.S., Filipek S., Wells J.W., Palczewski K., 2004, Biochemistry 43: 15643

    Article  CAS  Google Scholar 

  27. Terrillon S., Bouvier M., 2004, EMBO Rep. 5: 30

    Article  CAS  Google Scholar 

  28. Filizola M., Weinstein H., 2005, Curr. Opin. Drug. Disc Develop. 8: 577

    CAS  Google Scholar 

  29. Fotiadis D., Liang Y., Filipek S., Saperstein D.A., Engel A., Palczewski K., 2003, Nature 421: 127

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Mount Sinai School of Medicine, NYU, One Gustave L. Levy Place, Box 1218, New York, NY, 10029, USA

    Mihaly Mezei

  2. Department of Physiology & Biophysics, Weill Medical College of Cornell University, 1200 York Ave, New York, NY, 10021, USA

    Marta Filizola

Authors
  1. Mihaly Mezei
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  2. Marta Filizola
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Mezei, M., Filizola, M. TRAJELIX: A Computational Tool for the Geometric Characterization of Protein Helices During Molecular Dynamics Simulations. J Comput Aided Mol Des 20, 97–107 (2006). https://doi.org/10.1007/s10822-006-9039-1

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  • DOI: https://doi.org/10.1007/s10822-006-9039-1

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