Analysis of Water Molecules in the Hras-GTP and GDP Complexes with Molecular Dynamics Simulations

  • Takeshi MiyakawaEmail author
  • Ryota Morikawa
  • Masako Takasu
  • Akira Dobashi
  • Kimikazu Sugimori
  • Kazutomo Kawaguchi
  • Hiroaki Saito
  • Hidemi Nagao
Conference paper
Part of the Progress in Theoretical Chemistry and Physics book series (PTCP, volume 27)


In the Hras-GTP and GDP complexes, the coordination bonds between Mg2+ and oxygen atoms are very important. In this study, we use AMBER03 and our calculated force field parameters, and perform MD simulations of Hras-GTP and GDP complexes with water solvents. It is shown that the number of water molecules in the first hydration sphere is larger in GDP than in GTP. The duration time and the direction of water molecules in the first hydration sphere in GTP is not so different from those in GDP. It is shown that water molecules are distributed evenly around PG, although they are not distributed evenly around PB. This difference can be the reason why the hydrolysis of GTP in Hras-GTP is easier than the hydrolysis of GDP in Hras-GDP.


Water Molecule Angular Distribution Duration Time Radial Distribution Function Phosphorus Atom 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by JSPS KAKENHI Grant Number 24540442. The computations were in part carried out at the Research Center for Computational Science, Okazaki, Japan.


  1. 1.
    Alberts B, Johnson A, Lewis J, Raff M, Robertss K, Walter P (2002) Molecular biology of the cell, 5th edn. Garland, New York Google Scholar
  2. 2.
    Downward J (2003) Nat Rev Cancer 3:11–22 CrossRefGoogle Scholar
  3. 3.
    Goodsell DS (1999) Oncologist 4:263–264 Google Scholar
  4. 4.
    Pai EF, Krengel U, Petsko GA, Goody RS, Kabsch W, Wittinghofer A (1990) EMBO J 9:2351–2359 Google Scholar
  5. 5.
    Milburn MV, Tong L, deVos AM, Brünger A, Yamaizumi Z, Nishimura S, Kim SH (1990) Science 247:939–945 CrossRefGoogle Scholar
  6. 6.
    Coleman DE, Berghuis AM, Lee E, Linder ME, Gilman AG, Sprang SR (1994) Science 265:1405–1412 CrossRefGoogle Scholar
  7. 7.
    Frech M, Darden TA, Pedersen LG, Foley CK, Charifson PS, Anderson MW, Wittinghofer A (1994) Biochemistry 33:3237–3244 CrossRefGoogle Scholar
  8. 8.
    Glennon TM, Villa J, Warshel A (2000) Biochemistry 39:9641–9651 CrossRefGoogle Scholar
  9. 9.
    Langen R, Shweins T, Warshel A (1992) Biochemistry 31:8691–8696 CrossRefGoogle Scholar
  10. 10.
    Privé GG, Milburn MV, Tong L, de Vos AM, Yamaizumi Z, Nishimura S, Kim SH (1992) Proc Natl Acad Sci USA 89:3649–3653 CrossRefGoogle Scholar
  11. 11.
    Schweins T, Geyer M, Scheffzek K, Warshel A, Kalbitzer HR, Wittinghofer A (1995) Nat Struct Biol 2:36–44 CrossRefGoogle Scholar
  12. 12.
    Schweins T, Warshel A (1996) Biochemistry 35:14232–14243 CrossRefGoogle Scholar
  13. 13.
    Maegley KA, Admiraal SJ, Herschlag D (1996) Proc Natl Acad Sci USA 93:8160–8166 CrossRefGoogle Scholar
  14. 14.
    Admiraal SJ, Herschlag D (1995) Chem Biol 2:729–739 CrossRefGoogle Scholar
  15. 15.
    Herschlag D, Jencks WP (1989) J Am Chem Soc 111:7587–7596 CrossRefGoogle Scholar
  16. 16.
    Skoog MT, Jencks WP (1984) J Am Chem Soc 106:7597–7606 CrossRefGoogle Scholar
  17. 17.
    Allin C, Armadian MR, Wittinghofer A, Gerwert K (2001) Proc Natl Acad Sci USA 98:7754–7759 CrossRefGoogle Scholar
  18. 18.
    Allin C, Gerwert K (2001) Biochemistry 40:3037–3046 CrossRefGoogle Scholar
  19. 19.
    Cepus V, Scheidig AJ, Goody RS, Gerwert K (2001) Biochemistry 37:10263–10271 CrossRefGoogle Scholar
  20. 20.
    Du X, Frei H, Kim SH (2000) J Biol Chem 275:8492–8500 CrossRefGoogle Scholar
  21. 21.
    Wang JH, Xiao DG, Deng H, Webb MR, Callender R (1998) Biochemistry 37:11106–11116 CrossRefGoogle Scholar
  22. 22.
    Zhu G, Liu J, Terzyan S, Zai P, Li G, Zhang XC (2003) J Biol Chem 278:2452–2460 CrossRefGoogle Scholar
  23. 23.
    Cheng H, Sukal S, Deng H, Leyh TS, Callender R (2001) Biochemistry 40:4035–4043 CrossRefGoogle Scholar
  24. 24.
    Herschlag D, Jencks WP (1986) J Am Chem Soc 108:7938–7946 CrossRefGoogle Scholar
  25. 25.
    Foley CL, Pedersen LG, Charifson PS, Darden TA, Wittinghofer A, Pai EF, Andersen MW (1992) Biochemistry 31:4951–4959 CrossRefGoogle Scholar
  26. 26.
    Worth GA, Edge C, Richards WG (1995) J Mol Model 1:123–142 CrossRefGoogle Scholar
  27. 27.
    Mello LV, van Aalten DMF, Findlay JBC (1997) Protein Eng 10:381–387 CrossRefGoogle Scholar
  28. 28.
    Futatsugi N, Tsuda M (2001) Biophys J 81:3483–3488 CrossRefGoogle Scholar
  29. 29.
    Kobayashi C, Saito S (2010) Biophys J 99:3726–3734 CrossRefGoogle Scholar
  30. 30.
    Duan Y, Wu C, Chowdhury S, Lee MC, Xiong W, Zhang G, Yang R, Cieplak P, Luo R, Lee T, Caldwell J, Wang J, Kollman P (2003) J Comput Chem 24:1999–2012 CrossRefGoogle Scholar
  31. 31.
    Miyakawa T, Morikawa R, Takasu M, Sugimori K, Kawaguchi K, Saito H, Nagao H (2012) Prog Theory Chem Phys 26:525–543 CrossRefGoogle Scholar
  32. 32.
    Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) J Chem Phys 79:926–935 CrossRefGoogle Scholar
  33. 33.
    Ryckaert J-P, Ciccotti G, Berendsen HJC (1977) J Comput Phys 23:327–341 CrossRefGoogle Scholar
  34. 34.
    Adelman SA, Doll JD (1976) J Chem Phys 64:2375–2388 CrossRefGoogle Scholar
  35. 35.
    Grest GS, Kremer K (1986) Phys Rev A 33:3628–3631 CrossRefGoogle Scholar
  36. 36.
    Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR (1984) J Chem Phys 81:3684–3690 CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Takeshi Miyakawa
    • 1
    Email author
  • Ryota Morikawa
    • 1
  • Masako Takasu
    • 1
  • Akira Dobashi
    • 2
  • Kimikazu Sugimori
    • 3
  • Kazutomo Kawaguchi
    • 4
  • Hiroaki Saito
    • 4
  • Hidemi Nagao
    • 4
  1. 1.School of Life SciencesTokyo University of Pharmacy and Life SciencesHachiojiJapan
  2. 2.School of PharmacyTokyo University of Pharmacy and Life SciencesHachiojiJapan
  3. 3.Research Center for Higher EducationKanazawa UniversityKanazawaJapan
  4. 4.Institute of Science and EngineeringKanazawa UniversityKanazawaJapan

Personalised recommendations