Journal of Computer-Aided Molecular Design

, Volume 22, Issue 8, pp 553–561

Modeling dimerizations of transmembrane proteins using Brownian dynamics simulations

Article

Abstract

The dimerizations of membrane proteins, Outer Membrane Phospholipase A (OMPLA) and glycophorin A (GPA), have been simulated by an adapted Brownian Dynamics program. To mimic the membrane protein environment, we introduced a hybrid electrostatic potential map of membrane and water for electrostatic interaction calculations. We added a van der Waals potential term to the force field of the current version of the BD program to simulate the short-range interactions of the two monomers. We reduced the BD sampling space from three dimensions to two dimensions to improve the efficiency of BD simulations for membrane proteins. The OMPLA and GPA dimers predicted by our 2D-BD simulation and structural refinement is in good agreement with the experimental structures. The adapted 2D-BD method could be used for prediction of dimerization of other membrane proteins, such as G protein-coupled receptors, to help better understanding of the structures and functions of membrane proteins.

Keywords

Molecular modeling Brownian dynamics Molecular recognition Transmembrane protein Dimerization 

References

  1. 1.
    Heldin CH (1995) Cell 80(2):213CrossRefGoogle Scholar
  2. 2.
    Rios CD, Jordan BA, Gomes I, Devi LA (2001) Pharmacol Ther 92(2–3):71CrossRefGoogle Scholar
  3. 3.
    Milligan G (2001) J Cell Sci 114(Pt 7):265Google Scholar
  4. 4.
    Angers S, Salahpour A, Bouvier M (2002) Annu Rev Pharmacol Toxicol 42:409CrossRefGoogle Scholar
  5. 5.
    Bouvier M (2001) Nat Rev Neurosci 2(4):274CrossRefGoogle Scholar
  6. 6.
    George SR, O’Dowd BF, Lee SP (2002) Nat Rev Drug Discov 1(10):808CrossRefGoogle Scholar
  7. 7.
    Breitwieser GE (2004) Circ Res 94(1):17CrossRefGoogle Scholar
  8. 8.
    Milligan G (2006) Drug Discov Today 11(11–12):541CrossRefGoogle Scholar
  9. 9.
    Angers S, Salahpour A, Joly E, Hilairet S, Chelsky D, Dennis M, Bouvier M (2000) Proc Natl Acad Sci USA 97(7):3684CrossRefGoogle Scholar
  10. 10.
    Dinger MC, Bader JE, Kobor AD, Kretzschmar AK, Beck-Sickinger AG (2003) J Biol Chem 278(12):10562CrossRefGoogle Scholar
  11. 11.
    McVey M, Ramsay D, Kellett E, Rees S, Wilson S, Pope AJ, Milligan G (2001) J Biol Chem 276(17):14092Google Scholar
  12. 12.
    Fotiadis D, Liang Y, Filipek S, Saperstein DA, Engel A, Palczewski K (2003) Nature 421(6919):127CrossRefGoogle Scholar
  13. 13.
    Liang Y, Fotiadis D, Filipek S, Saperstein DA, Palczewski K, Engel A (2003) J Biol Chem 278(24):21655CrossRefGoogle Scholar
  14. 14.
    Fotiadis D, Liang Y, Filipek S, Saperstein DA, Engel A, Palczewski K (2004) FEBS Lett 564(3):281CrossRefGoogle Scholar
  15. 15.
    Cheng ZJ, Miller LJ (2001) J Biol Chem 276(51):48040Google Scholar
  16. 16.
    Kota P, Reeves PJ, Rajbhandary UL, Khorana HG (2006) Proc Natl Acad Sci USA 103(9):3054CrossRefGoogle Scholar
  17. 17.
    Davies A, Schertler GF, Gowen BE, Saibil HR (1996) J Struct Biol 117(1):36CrossRefGoogle Scholar
  18. 18.
    Schertler GF, Hargrave PA (1995) Proc Natl Acad Sci USA 92(25):11578CrossRefGoogle Scholar
  19. 19.
    Davies A, Gowen BE, Krebs AM, Schertler GF, Saibil HR (2001) J Mol Biol 314(3):455CrossRefGoogle Scholar
  20. 20.
    Guo W, Shi L, Filizola M, Weinstein H, Javitch JA (2005) Proc Natl Acad Sci USA 102(48):17495CrossRefGoogle Scholar
  21. 21.
    Filizola M, Weinstein H (2005) Febs J 272(12):2926CrossRefGoogle Scholar
  22. 22.
    Filizola M, Weinstein H (2002) Biopolymers 66(5):317CrossRefGoogle Scholar
  23. 23.
    Filizola M, Olmea O, Weinstein H (2002) Protein Eng 15(11):881CrossRefGoogle Scholar
  24. 24.
    Smith GR, Sternberg MJ (2002) Curr Opin Struct Biol 12(1):28CrossRefGoogle Scholar
  25. 25.
    Ouporov IV, Knull HR, Thomasson KA (1999) Biophys J 76(1 Pt 1):17Google Scholar
  26. 26.
    Pearson DC Jr, Gross EL (1998) Biophys J 75(6):2698Google Scholar
  27. 27.
    Lowe SL, Adrian C, Ouporov IV, Waingeh VF, Thomasson KA (2003) Biopolymers 70(4):456CrossRefGoogle Scholar
  28. 28.
    Cui M, Shen J, Briggs JM, Luo X, Tan X, Jiang H, Chen K, Ji R (2001) Biophys J 80(4):1659Google Scholar
  29. 29.
    Cui M, Shen J, Briggs JM, Fu W, Wu J, Zhang Y, Luo X, Chi Z, Ji R, Jiang H, Chen K (2002) J Mol Biol 318(2):417CrossRefGoogle Scholar
  30. 30.
    Fu W, Cui M, Briggs JM, Huang X, Xiong B, Zhang Y, Luo X, Shen J, Ji R, Jiang H, Chen K (2002) Biophys J 83(5):2370CrossRefGoogle Scholar
  31. 31.
    Huang X, Liu H, Cui M, Fu W, Yu K, Chen K, Luo X, Shen J, Jiang H (2004) Curr Pharm Des 10(9):1057CrossRefGoogle Scholar
  32. 32.
    Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) Nucleic Acids Res 28(1):235CrossRefGoogle Scholar
  33. 33.
    Snijder HJ, Ubarretxena-Belandia I, Blaauw M, Kalk KH, Verheij HM, Egmond MR, Dekker N, Dijkstra BW (1999) Nature 401(6754):717CrossRefGoogle Scholar
  34. 34.
    Fiser A, Sali A (2003) Bioinformatics 19(18):2500CrossRefGoogle Scholar
  35. 35.
    Fiser A, Do RK, Sali A (2000) Protein Sci 9(9):1753Google Scholar
  36. 36.
    MacKenzie KR, Prestegard JH, Engelman DM (1997) Science 276(5309):131CrossRefGoogle Scholar
  37. 37.
    Northrup SH, Laughner T, Stevenson G (1999) MacroDox macromolecular simulation program. Tennessee Technological University, Department of Chemistry, Cookeville, TNGoogle Scholar
  38. 38.
    Northrup SH, Boles JO, Reynolds JCL (1987) J Phys Chem 91:5991CrossRefGoogle Scholar
  39. 39.
    Northrup SH, Thomasson KA, Miller CM, Barker PD, Eltis LD, Guillemette JG, Inglis SC, Mauk AG (1993) Biochemistry 32(26):6613CrossRefGoogle Scholar
  40. 40.
    Smoluchowski MV (1917) Z Phys Chem 92:129Google Scholar
  41. 41.
    Ermak DL, McCammon JA (1978) J Chem Phys 69:1352CrossRefGoogle Scholar
  42. 42.
    Warwicker J, Watson HC (1982) J Mol Biol 157(4):671CrossRefGoogle Scholar
  43. 43.
    Gabdoulline RR, Wade RC (1998) Methods 14(3):329CrossRefGoogle Scholar
  44. 44.
    Nelder JA, Mead R (1965) Comput J 7:308Google Scholar
  45. 45.
    Landolt-Marticorena C, Williams KA, Deber CM, Reithmeier RA (1993) J Mol Biol 229(3):602CrossRefGoogle Scholar
  46. 46.
    Arkin IT, Brunger AT (1998) Biochim Biophys Acta 1429(1):113Google Scholar
  47. 47.
    Killian JA, von Heijne G (2000) Trends Biochem Sci 25(9):429CrossRefGoogle Scholar
  48. 48.
    Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) J Comput Chem 19:1639CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.Department of Structural and Chemical BiologyMount Sinai School of Medicine, New York UniversityNew YorkUSA

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