A Study on The Effect of Temperature on Human Prion Protein Structure through Molecular Dynamic Simulation

Authors

1 M.Sc. Student, Department of Physical Chemistry, School ofBasic Sciences, Islamic Azad University, Science and Research Branch Khuzestan, Ahvaz, Iran

2 Assistant Professor, Department of Biology, School of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran

Abstract

Background & Aims: The normal form of the prion protein is called PrPC and its infectious form is called PrPSc. This protein functions like a crystallized core for the transformation of PrPc into an abnormal PrPSc. The aim of the present study was to investigate the effect of temperature on human prion protein structure through molecular dynamic simulation. Methods: In this research, the GROMACS software was used in Linux operating system for simulation. After performing molecular dynamic simulation, the parameters were extracted from the trajectory and data analysis was performed. The results were entered into an Excel spreadsheet and figures and tables were designed in this software. Results: In this study, the effect of temperature and density of sodium chloride on human prion protein stability was studied by molecular dynamics simulation during 10 nanoseconds. The results of this study show that, with 0.1 molar sodium chloride (natural density in tissues), a change in the temperature of environment from 37 ℃ (natural temperature of the body) to 27 ℃ or 47 ℃ leads to structural changes. This can be studied using root mean squared deviation (RMSD) of protein root and structure, radius of gyration of hydrophobic accessible surface, and distances between ionic groups of protein. Conclusion: The results of this study show that in 0.1 molar sodium chloride and 37 ℃, protein regains its natural structure and an increase or decrease in temperature causes protein to change to an abnormal structure. This can be the cause of the abnormal structure of this protein observed in some illness like mad cow diseases. It is noteworthy that an increase in temperature is more effective in causing this anomaly than a decrease.

Keywords


  1. Sakaguchi S. Molecular biology of prion protein and its first homologous protein. J Med Invest 2007; 54(3-4): 211-23.
  2. Okimoto N, Yamanaka K, Suenaga A, Hirano Y, Futatsugi N, Narumi, et al. Molecular Dynamics Simulations of Prion Proteins - Effect of Ala117? Val mutation-. Chem-Bio Informatics Journal 2003; 3(1): 1-11.
  3. Prusiner SB. Molecular biology of prion diseases. Science 1991; 252(5012): 1515-22.
  4. Trevitt CR, Singh PN. Variant Creutzfeldt-Jakob disease: pathology, epidemiology, and public health implications. Am J Clin Nutr 2003; 78(3 Suppl): 651S-6S.
  5. Ironside JW. Variant Creutzfeldt-Jakob disease: risk of transmission by blood transfusion and blood therapies. Haemophilia 2006; 12(Suppl 1): 8-15.
  6. Will RG. Acquired prion disease: iatrogenic CJD, variant CJD, kuru. Br Med Bull 2003; 66: 255-65.
  7. Wadsworth JD, Hill AF, Beck JA, Collinge J. Molecular and clinical classification of human prion disease. Br Med Bull 2003; 66: 241-54.
  8. Sekijima M, Motono C, Yamasaki S, Kaneko K, Akiyama Y. Molecular dynamics simulation of dimeric and monomeric forms of human prion protein: insight into dynamics and properties. Biophys J 2003; 85(2): 1176-85.
  9. Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJ. GROMACS: fast, flexible, and free. J Comput Chem 2005; 26(16): 1701-18.
  10. Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics. J Mol Graph 1996; 14(1): 33-8.