Calculation of pathways for the conformational transition between the GTP- and GDP-bound states of the Ha-ras-p21 protein: Calculations with explicit solvent simulations and comparison with calculations in vacuum

Proteins: Structure, Function and Genetics

Volumn 28, Issue 3, 1997, Pages 434-451

  Díaz, José Fernando ^a   Wroblowski, Berthold ^a   Schlitter, Jürgen ^b   Engelborghs, Yves ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b RUHR UNIVERSITY BOCHUM   (Germany)

Author keywords

G proteins; GROMOS; Molecular dynamics; Molecular switch; Oncogenes; TMD algorithm

Indexed keywords

GUANINE NUCLEOTIDE BINDING PROTEIN; PROTEIN P21; RAS PROTEIN;

ARTICLE; BINDING SITE; CALCULATION; CONFORMATIONAL TRANSITION; MATHEMATICAL ANALYSIS; MOLECULAR DYNAMICS; MOLECULAR RECOGNITION; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CONFORMATION;

CATIONS, DIVALENT; GUANOSINE DIPHOSPHATE; GUANOSINE TRIPHOSPHATE; HYDROGEN BONDING; MAGNESIUM; MATHEMATICAL COMPUTING; PROTEIN BINDING; PROTEIN CONFORMATION; PROTO-ONCOGENE PROTEINS P21(RAS); SOLVENTS; THERMODYNAMICS;

EID: 0242618314     PISSN: 08873585     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1097-0134(199707)28:3<434::AID-PROT12>3.0.CO;2-I     Document Type: Article

References (64)

1. Schlegel, H.B. Optimization of equilibrium geometries and transition structures. Adv. Chem. Phys. 67:249-286, 1987.
2. Bell, S., Crighton, J.S. Locating transition states. J. Chem. Phys. 80:2464-2475, 1984.
3. Elber, R., Karplus, M. A method for determining reaction paths in large molecules: Application to mioglobin. Chem. Phys. Lett. 139:375-380, 1987.
4. Czerminski, R., Elber, R. Self-avoiding walk between two fixed points as a tool to calculate reaction paths in large molecular systems. Int. J. Quantum Chem. 824:167, 1990.
5. Engels, M., Jacoby, E., Krüger, P., Schlitter, J., Wollmer, A. The T〈-〉R structural transition of insulin; pathways suggested by targeted energy minimization. Protein Eng. 5:669-677, 1992.
6. Smart, O.S. A new method to calculate reaction paths for conformational transitions of large molecules. Chem. Phys. Lett. 222:503-512, 1994.
7. Ech-Cherif El-Kettani, M.A., Dump, J. Theoretical determination of conformational paths in citrate synthase. Biopolymers 32:561-574, 1992.
8. Elber, R. Calculation of the potential of mean force using molecular dynamics with linear constraints: An application to a conformational transition in a solvated dipeptide. J. Chem. Phys. 93:4312-4321, 1990.
9. Schlitter, J., Engels, M., Krüger, P., Jacoby, E., Wollmer, A. Targeted molecular dynamics simulation of conformational change - Application to the T〈-〉R transition in insulin. Mol. Sim. 10:291-309, 1993.
10. Schlitter, J., Engels, M., Krüger, P. Targeted molecular dynamics: A new approach for searching pathways of conformational transitions. J. Mol. Graphics 12:84-89, 1994.
11. Ech-Cherif El-Kettani, M.A., Zakrzewska, K., Durup, J., Lavery, R. An analysis of the conformational paths of citrate synthase. Proteins 16:393-407, 1993.
12. Smart, O.S., Goodfellow, J.M., Wallace, B.A. The pore dimensions of gramicidin A, Biophys. J. 65:2455-2460, 1993.
13. Bourne, H.R., Sanders, D.A., McCormick, F. The GTPase superfamily: A conserved switch for diverse cell functions. Nature 348:125-132, 1990.
14. Bourne, H.R., Sanders, D.A., McCormick, F. The GTPase superfamily: Conserved structure and molecular mechanism. Nature 349:117-126, 1991.
15. Barbacid, M. ras Genes. Annu. Rev. Biochem. 56:779-827, 1987.
16. Tong, L.A., de Vos, A.M., Milburn, M.V., Kim, S.H. Crystal structures at 2.2 Å resolution of the catalytic domains of normal ras protein and an oncogenic mutant complexed with GDPJ. Mol. Biol. 217:503-516, 1991.
17. Pai, E.R, Krengel, U., Petsko, G.A., Goody, R.S., Kabsh, W., Wittinghofer, A. Refined crystal structure of the triphosphate conformation of H-ras-p21 at 1.35 Å resolution: Implications for the mechanism of GTP hydrolysis. EMBO J. 9:2351-2359, 1990.
18. Kaziro, Y. The role of guanosine 5′-triphosphate in polypeptide chain elongation. Biochem. Biophys. Acta 505:95-127, 1978.
19. Stryer, L., Bourne, H.R. G-proteins a family of signal transducers. Annu. Rev. Cell. Biol. 2:391-419, 1986.
20. Gillman, A.G. G-proteins: Transducers of receptor-generated signals. Annu. Rev. Biochem. 56:615-649, 1987.
21. Bos, J.L: ras-Oncogenes in human cancer. Cancer Res. 49:4682-4689, 1989.
22. McCormick, F. Activators and effectors of ras p21 proteins. Curr. Opin. Gen. Dev. 4:71-76, 1994.
23. Adari, H., Lowy, D.R., Willumsen, B.M., Der, C.J., McCormick, F. Guanosine triphosphatase activating protein (GAP) interacts with the ras-p21 effector binding domain. Science 240:518-521, 1988.
24. Langen, R., Schweins, T., Warshel, A. On the mechanism of guanosine triphosphate hydrolysis in ras p21 proteins. Biochemistry 31:8691-8696, 1992.
25. H-ras. An experimental and theoretical study. Biochemistry 33:3237-3244, 1994.
26. Wittinghoffer, A., Pai, E.F. The structure of ras protein: A model for a universal molecular switch. Trends Biochem Sci. 16:382-387, 1991.
27. Brandt-Rauf, P.W., Carty, R.P., Carucci, J., Avitable, M., Lubowsky, J., Pincus, M.R. Conformational effects of the substitution of ARG for GLY 13 in the ras oncogen-encoded p21 protein. J. Protein Chem. 7:349-354, 1988.
28. Valencia, A., Chardin, P., Wittinghofer, A., Sander, C. The ras protein family: Evolutionary tree and role of conserved amino acids. Biochemistry 30:4637-4648, 1991.
29. Díaz, J.F, Wroblowski, B., Engelborghs, Y. Molecular dynamics simulation of the solution structures of ras-p21 GDP and GTP complexes. Flexibility, possible hinges, and levers of the conformational transition. Biochemistry 34: 12038-12047, 1995.
30. Dagget, V., Levitt, M. Realistic simulations of native-protein dynamics in solution and beyond. Annu. Rev. Biomol. Struct. 22:353-380, 1993.
31. Birktoft, J.J., Blow, D.M. Structure of crystalline α-chymotrypsin. V. The atomic structure of tosil, α-chymotrypsin at 2 Å. J. Mol. Biol. 68:187-240, 1972.
32. McCammon, J.A., Gelin, B.R., Karplus, M.: Dynamics of folded proteins. Nature 267:585-590, 1977.
33. Levitt, M., Lifson, S. Refinement of protein conformations using a macromolecular energy minimization procedure. J. Mol. Biol. 46:269-279, 1969.
34. Ryckaert, J.P., Ciccotti, G., Berendsen, H.J.C. Numerical integration of cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. J. Comput. Phys. 23:327-341, 1977.
35. Berendsen, H.J.C., Postma, J.P.M., van Gunsteren, W.F., Dinola, A., Haak, J.R. Molecular dynamics with coupling to an external bath. J. Chem. Phys. 81:3684-3690, 1984.
36. Diamond, R.J. Real space refinement of the structure of hen-white lysozyme. J. Mol. Biol. 82:371-391, 1974.
37. Kraulis, P.J., Domaille, P.J., Campbell-Burk, S.L., Van Aken, T., Laue, E.D. Solution structure and dynamics of ras p21-GDP determined by heteronuclear three- and four-dimensional NMR spectroscopy. Biochemistry 33:3515-3531, 1994.
38. van Gunsteren, W.F., Berendsen, H.J.C. Program system GROMOS 87. Distributed by: Biomos biomolecular software b. v. Laboratory of Physical Chemistry University of Groningen, 1987.
39. Krüger, P., Lüke, M., Szameit, A. SIMLYS - A software package for trajectory analysis of molecular dynamics simulations. Comput. Phys. Commun. 62:371-380, 1991.
40. Krüger, P., Szameit, A. SIMLYS version 2.0. Comput. Phys. Commun. 72P:265-268, 1992.
41. Vriend, G. WHAT IF: A molecular modeling and drug design program. J. Mol. Graphics 8:52-56, 1990.
42. Van Gunsteren, W.F. Molecular dynamics and stochastic dynamics simulation: A primer. In: 'Computer Simulations of Biomolecular Systems. Vol. 2. van Gunsteren, W.F., Weiner, P.K., Wilkinson, A.J. (eds.). Leiden: ESCOM, 1993: 3-36.
43. 10 Helix versus a-helix: A molecular dynamics study of conformational preferences of Aib and alanine. J. Am. Chem. Soc. 116:11915-11921, 1994.
44. Mulders, T., Krüger, P., Swegat, W., Schlitter, J. Free energy as the potential of mean constraint force. J. Chem. Phys. 104:4869-4870, 1996.
45. Jacoby, E., Krüger, P., Schlitter, J., Wollmer, A. Simulation of a complex protein structural change. The T〈-〉R transition in the insulin hexamer. Protein Eng. 9:113-125, 1996.
46. Kraulis, P.J. MOLSCRIPT: A program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 24:946-950, 1991.
47. Dykes, D.C., Friedman, F.K., Dykes, S.L., Murphy, R.B., Brand-Rauf, P.W., Pincus, M.R. Molecular dynamics of the ras gene-encoded p21 protein: Identification of flexible regions and possible effector domains. J. Biomol. Struct. Dyn. 11:443-458, 1993.
48. Schlichting, I., Raap, G., Almo, S., Wilson, K., Pai, E., Petsko, G.A., Goody, R.S. Time-resolved X-ray crystallographic study of the conformational change in Ha-ras p21 protein on GTP hydrolysis. Nature 345:309-315, 1990.
49. Van Gunsteren, W.F., Berendsen, H.J.C. Computer simulation as a tool for tracing the conformational differences between proteins in solution and in crystalline state. J. Mol. Biol. 176:559-564, 1984.
50. Krengel, U., Schlichting, I., Scherer, A., Schumann, R., Frech, M., John, J., Kabsh, W., Pai, E.F., Wittinghofer, A. Three dimensional structure of H-ras-p21 mutants: Molecular basis for their inability to function as signal switch molecules. Cell 62:539-548, 1990.
51. Clanton, D.J., Lu, Y., Blair, D.G., Shih, T.Y. Structural significance of the GTP-binding domain of ras-p21 studied by site-directed mutagenesis. Mol. Cell. Biol 7:3092-3097, 1987.
52. Liwo, A., Gibson, K.D., Scheraga, H.A., Brandt-Rauf, P.W., Monaco, R., Pincus, M.R. Comparison of the low energy conformations of an oncogenic and a non-oncogenic p21 protein, neither of which binds GTP of GDP. J. Protein Chem. 13:237-251, 1994.
53. Bigay, J., Deterre, P., Pfister, C., Chabre, M. Fluoride complexes of aluminum or beryllium act on G-proteins as reversible bound analogues of the γ-phosphate. EMBO J. 6:2907-2913, 1987.
54. Mittal, R., Ahmadian, M.R., Goody, R.S., Wittinghofer, A. Formation of a transition-state analog of the ras GTPase reaction by ras-GDP, tetrafluoroaluminate and GTPase-activating proteins. Science 237:115-117, 1996.
55. Polakis, P., McCormick, F. Structural requirements for the interaction with GAP exchange factors, and its biological effector target. J. Biol. Chem. 268:9157-9160, 1993.
56. Willumsen, B.M., Adari, H., Zhang, K., Papageorge, A.G., Stone, J.C., McCormick, F., Lowy, D.R. In: 'The Guanine Nucleotide Binding Proteins: Common Structural and Functional Properties.' Bosch, L., Kraal, B., Parmeggiani, A. (eds.). New York: Plenum Press, 1989:165-177.
57. Stone, J.C., Blanchard, R.A. Genetic definition of the ras-effector elements. Mol. Cell. Biol. 11:6158-6165, 1991.
58. Mistou, M.Y., Jacquet, E., Poullet, P., Rensland, H., Gideon, P., Schlichting, I. Wittinghofer, A., Parmeggiani, A. Mutations of Ha-ras p21 that define important regions for the molecular mechanism of the SDC25 C-domain, a guanine nucleotide dissociation stimulator. EMBO J. 11: 2391-2397, 1992.
59. Sung, Y.J, Carter, M., Zhong, J.M., Hwang, Y.W. Mutagenesis of the H-ras-p21 at glycine 60 disrupts GTP-induced conformational change. Biochemistry 34:3470-3477, 1995.
60. Hwang, M.C., Sung, Y., Hwang, Y.W. The differential effects of the Gly-60 to Ala mutation on the interaction of H-Ras p21 with different downstream targets. J. Biol. Chem. 271:8196-8202, 1996.
61. Sigal, I.B., Gibbs, J.B., D'alonzo, J.D., Scolnick, E.M.: Identification of effector residues and neutralizing epitopes of Ha-ras-encoded p21. Proc. Natl. Acad. Sci. USA 83:4725-4729, 1986.
62. Sigal, I.B., Gibbs, J.B., D'alonzo, J.D., Temeles, G.L., Wolanski, B.S., Socher, S.H., Scolnick, E.M. Mutant ras-encoded proteins with altered nucleotide binding exert dominant biological effects. Proc. Natl. Acad. Sci. USA 83:952-956, 1986.
63. Feig, L.A., Pan, B.T., Roberts, T.M., Cooper, G.M. Isolation of ras GTP-binding mutants using an in situ colony binding assay. Proc. Natl. Acad. Sci. USA 83:4607-4611, 1986.
64. Hu, J.S., Redfield, A.G. Mapping the nucleotide-dependent conformational change of human N-ras p21 in solution by heteronuclear-edited proton-observed NMR methods. Biochemistry 32:6763-6772, 1993.