The Potentials of the Atoms around Mg2+ in the H-ras GTP and GDP Complexes

  • T. Miyakawa
  • R. Morikawa
  • M. Takasu
  • K. Sugimori
  • K. Kawaguchi
  • H. Saito
  • H. Nagao
Conference paper
Part of the Progress in Theoretical Chemistry and Physics book series (PTCP, volume 26)


We have studied the quantum state around the Mg2+ ion in the H-ras GTP and H-ras GDP complexes in order to understand the hydrolysis of GTP to GDP in the H-ras complex, which plays a key role in overcoming human cancer. We calculated the force fields and atomic charges around the Mg2+ ion in the H-ras GTP and H-ras GDP complexes at the B3LYP level, using a basis functional set 6-31G**. The calculations were performed in the subsystem consisting of the bases or the molecules containing the oxygen having a coordinate bond to the Mg2+ ion. They showed that the oxygen atoms in both GTP and GDP bind tightly to the Mg2+ ion, although the oxygen atoms in H2O bind loosely. We have also performed MD simulations of the H-ras GTP and H-ras GDP complexes in solution, using these potential parameters. We showed that the structure differences between H-ras GTP and H-ras GDP are found mainly in loop 2 and loop 4.


Dihedral Angle Atomic Charge Extended Form Guanine Nucleotide Amber Force Field 
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This work was partially funded by Grant-in-Aid for Scientific Research.


  1. 1.
    Downward J (2003) Nat Rev Cancer 3:11–22CrossRefGoogle Scholar
  2. 2.
    Pai EF, Krengel U, Petsko GA, Goody RS, Kabsch W, Wittinghofer A (1990) EMBO J 9: 2351–2359Google Scholar
  3. 3.
    Milburn MV, Tong L, deVos AM, Brünger A, Yamaizumi Z, Nishimura S, Kim SH (1990) Science 247:939–945CrossRefGoogle Scholar
  4. 4.
    White MA, Nicolette C, Minden A, Polverino A, Linda VA, Karin M, Wigler MH (1995) Cell 80:533–541CrossRefGoogle Scholar
  5. 5.
    Sung YJ, Carter M, Zhong JM, Hwang YW (1995) Biochemistry 34:3470–3477CrossRefGoogle Scholar
  6. 6.
    Hwang MCC, Sung YJ, Hwang YW (1996) J Biol Chem 271:8196–8202CrossRefGoogle Scholar
  7. 7.
    Rodriguez-Viciana P, Warne PH, Khwaja A, Marte BM, Pappin D, Das P, Waterfield MD, Ridley A, Dowanward J (1997) Cell 89:457–467CrossRefGoogle Scholar
  8. 8.
    Spoerner M, Herrmann C, Vetter IR, Kalbitzer HR, Wittinghofer A (2001) Proc Natl Acad Sci U S A 98:4944–4949CrossRefGoogle Scholar
  9. 9.
    Fiordalisi JJ, Holly SP, Johnson RL II, Parise LV, Cox AD (2002) J Biol Chem 277, 10813–10823CrossRefGoogle Scholar
  10. 10.
    Ford B, Skowronek K, Boykevisch S, Bar-Sagi D, Nassar N (2005) J Biol Chem 280: 25697–25705CrossRefGoogle Scholar
  11. 11.
    Duan Y, Wu C, Chowdhury S, Lee MC, Xiong G, Zhang W, Yang R, Cieplak P, Luo R, Lee T, Caldwell J, Wang J, Kollman P (2003) J Comput Chem 24:1999–2012CrossRefGoogle Scholar
  12. 12.
    Foley CL, Pedersen LG, Charifson PS, Darden TA, Wittinghofer A, Pai EF, Andersen MW (1992) Biochemistry 31:4951–4959CrossRefGoogle Scholar
  13. 13.
    Frisch MJ, Head - Gordon M, Schlegel HB, Raghavarchi K, Binkley JS, Gonzalez C, Defrees DF, Fox DJ, Whiteside RA, Seeger R, Melius CF, Baker J, Martin R, Kahn LR, Stewart JJP, Fluder EM, Topiol S, Pople JA (1988) GAUSSIAN88, Gaussian Inc., Pittsburgh, 200 Fifth Ave., Waltham, MA 02154Google Scholar
  14. 14.
    Worth GA, Edge C, Richards WG (1995) J Mol Model 1:123–142CrossRefGoogle Scholar
  15. 15.
    Mello LV, van Aalten DMF, Findlay JBC (1997) Protein Eng 10:381–387CrossRefGoogle Scholar
  16. 16.
    Futatsugi N, Tsuda M (2001) Biophys J 81:3483–3488CrossRefGoogle Scholar
  17. 17.
    Kobayashi C, Saito S (2010) Biophys J 99:3726–3734CrossRefGoogle Scholar
  18. 18.
    Meagher KL, Redman LT, Carlson HA (2003) J Comput Chem 24:1016–1025CrossRefGoogle Scholar
  19. 19.
    Frisch M et al (2009) Gaussian 09, Revision A.01, Gaussian Inc., Walling-fordGoogle Scholar
  20. 20.
    Singh UC, Kollman PA (1984) J Comp Chem 5:129–145CrossRefGoogle Scholar
  21. 21.
    Case DA, Darden TA, Cheatham TE III, Simmerling CL, Wang J, Duke RE, Luo R, Walker RC, Zhang W, Merz KM, Roberts B, Wang B, Hayik S, Roitberg A, Seabra G, Kolossváry I, Wong KF, Paesani F, Vanicek J, Liu J, Wu X, Brozell SR, Steinbrecher T, Gohlke H, Cai Q, Ye X, Wang J, Hsieh M-J, Cui G, Roe DR, Mathews DH, Seetin MG, Sagui C, Babin V, Luchko T, Gusarov S, Kovalenko A, Kollman PA (2010) AMBER11, University of California, San FranciscoGoogle Scholar
  22. 22.
    Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) J Chem Phys 79:926–935CrossRefGoogle Scholar
  23. 23.
    Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR (1984) J Chem Phys 81:3684–3690CrossRefGoogle Scholar
  24. 24.
    Shima F, Ijiri Y, Muraoka S, Liao J, Ye M, Araki M, Matsumoto K, Yamamoto N, Sugimoto T, Yoshikawa Y, Kumasaka T, Yamamoto M, Tamura A, Kataoka T (2010) Ras Protein J Biol Chem 285:22696–22705Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • T. Miyakawa
    • 1
  • R. Morikawa
    • 1
  • M. Takasu
    • 1
  • K. Sugimori
    • 2
  • K. Kawaguchi
    • 3
  • H. Saito
    • 3
  • H. Nagao
    • 3
  1. 1.School of Life SciencesTokyo University of Pharmacy and Life SciencesHachioji, TokyoJapan
  2. 2.Department of Physical Therapy, Faculty of Health SciencesKinjo UniversityHakusanJapan
  3. 3.Institute of Science and EngineeringKanazawa UniversityKakuma, KanazawaJapan

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