Hostname: page-component-745bb68f8f-f46jp Total loading time: 0 Render date: 2025-02-05T06:05:18.249Z Has data issue: false hasContentIssue false
  • English
  • Français

Fast Simulation Protocol for Protein Structural Transitions: Modeling of the Relationship of Structure and Function

Published online by Cambridge University Press:  15 March 2011

Arun K. Setty  and
D. M. Zuckerman
Arun K. Setty
Affiliation:
Center for Computational Biology and Bioinformatics and Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh
D. M. Zuckerman
Affiliation:
Center for Computational Biology and Bioinformatics and Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh
Get access

Abstract

An approach is developed to study the dynamics of protein conformational transitions in depth. A computational (Monte Carlo) approach based on a united residue model is used. Unbiased transitions between the Apo and Holo conformations/states of calmodulin are observed at the rate of 1 per day per processor. A series of models of increasing complexity is studied, accounting for hydrophobic interactions and calcium binding. Details of the transitional region and structural information about intermediate states are obtained. Statistically converged ensembles of transitions are obtained in a reasonable real time period.

Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 826: Symposium V – Proteins as Materials , 2004 , V3.5
Copyright
Copyright © Materials Research Society 2004

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

[1] Krebs, W. G. and Gerstein, M., Nucleic Acids Res., 28, 1665 (2000).Google Scholar
[2] Gerstein, M. and Krebs, W., Nucleic Acids Res., 26, 4280 (1998).Google Scholar
[3] Echols, N., Milburn, D. and Gerstein, M., Nucleic Acids Res., 31, 478 (2003).Google Scholar
[4] Harvey, S. C. and Gabb, H. A., Biopolymers, 33, 1167 (1993).Google Scholar
[5] Schlitter, J., Engels, M., Kruger, P. et al. , Molec. Sim., 10, 291, 1993).Google Scholar
[6] Zuckerman, D.M., J. Phys. Chem. B, in press.Google Scholar
[7] Ueda, Y., Taketomi, H., and Go, N., Int. J. Peptide Protein Res., 7, 445 (1975).Google Scholar
[8] Ueda, Y., Taketomi, H., and Go, N., Biopolymers, 17, 1531 (1978).Google Scholar
[9] Tobi, D., Shafran, G., Linial, N. and Elber, R., Proteins, 40, 71 (2000).Google Scholar
[10] Lau, K. F. and Dill, K. A., Macromolecules, 22, 3986, (1989).Google Scholar
[11] Chin, D. and Means, A. R., Trends in Cell Biol., 10, 322 (2000).Google Scholar
[12] Peterson, B. Z., DeMaria, C. D. and Yue, D. T., Neuron, 22, 549 (1999).Google Scholar
[13] Eldk, L. Van and Watterson, D. M., Calmodulin and signal transduction, Academic, San Diego, 1998.Google Scholar
[14] Cohen, P. and Klee, C. B., eds., Elsevier, Amsterdam, 1988.Google Scholar
[15] Eldik, L. J. van and Watterson, D. M., eds., Calmodulin and signal transduction, Academic Press, New York, 1998.Google Scholar
[16] Babu, Y.S., Bugg, C.E. and Cook, W.J., J. Molec. Bio., 204, 191 (1988).Google Scholar
[17] Strynadka, N. C. J. and James, M. N. G., Annu. Rev. Biochem 58, 951 (1989).Google Scholar
[18] Falke, J. J., Drake, S. K. et al. Q. Rev. Biophys., 27, 219 (1994).Google Scholar
[19] Ikura, M., Trends Biochem. Sci., 21, 14 (1996).Google Scholar
[20] Crivici, A. and Ikura, M., Annu. Rev. Biophys. Biomol. Struct. 24, 85 (1995).Google Scholar
[21] Kataoka, M., Head, J., Seaton, B. and Engelman, D., Proc. Natl. Acad. Sci. 86, 6944 (1989).Google Scholar
[22] Matsushima, N., Izumi, Y. et al. , J. Biochem. 105, 883 (1989).Google Scholar
[23] Meador, W. E., Means, A. R. and Quiocho, F. A., Science 257, 1251 (1992).Google Scholar
[24] Ikura, M., Science, 256, 632 (1992).Google Scholar
[25] Setty, A. K. and Zuckerman, D. M., in preparation.Google Scholar
[26] Clarke, J. and Itzhaki, L. S., Curr. Opin. Struct. Biol. 8, 112 (1998).Google Scholar
[27] Fersht, A., Structure and Mechanism in Protein Science, W. H. Freeman & Company, New York (1999).Google Scholar
[28] Li, R. and Woodward, C., Protein Sci., 8, 1571 (1999).Google Scholar
[29] Hoang, L. et al. , Proc. Natl. Acad. Sci., U.S.A., 99, 12173 (2002).Google Scholar
[30] Setty, A. K. and Zuckerman, D. M., in preparation.Google Scholar
[31] Hummer, G., J. Chem. Phys. 120, 516 (2004).Google Scholar
[32] Fallon, J. L. and Quiocho, F. A., Structure 11, 1303 (2003)Google Scholar