Abstract
The confinement of the metalloenzyme organophosphorous hydrolase in functionalized mesoporous silica (FMS) enhances the stability and increases catalytic specific activity by 200% compared to the enzyme in solution. The mechanism by which these processes take place is not well understood. We have developed macroscopic and coarse-grain models of confinement to provide insights into how the nanocage environment steers enzyme conformational dynamics towards enhanced stability and enzymatic activity. The structural dynamics of organophosphorous hydrolase under the two confinement models are very distinct from each other. Comparisons of the present simulations show that only one model leads to an accurate depiction of the internal dynamics of the enzyme.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Cao, L.: Immobilized Enzymes: science or art. Current Opinion in Chemical Biology 9, 217–226 (2005)
Lei, C., Shin, Y., Liu, J., Ackerman, E.J.: Entrapping enzyme in a functionalized nanoporous support. Journal of the American Chemical Society 124, 11242–11243 (2002)
Omburo, G.A., Kuo, J.M., Mullins, L.S., Raushel, F.M.: Characterization of the zinc binding site of bacterial phosphotriesterase. Journal of Biological Chemistry 267, 13278–13283 (1992)
Rochu, D., Renault, F., Viguille, N., Crouzier, D., Froment, M.T., Masson, P.: Contribution of the active-site metal cation to the catalytic activity and to the conformational stability of phosphotriesterase: temperature- and pH-dependence. Biochemical Journal 380, 627–633 (2004)
Raushel, F.M.: Bacterial detoxification of organophosphate nerve agents. Current Opinion in Microbiology 5, 288–295 (2002)
Bismuto, E., Martelli, P.L., Maio, A.D., Mita, D.G., Irace, G., Casadio, R.: Effect of molecular confinement on internal enzyme dynamics: Frequency domain fluorometry and molecular dynamics simulation studies. Biopolymers 67, 85–95 (2002)
Bolis, D., Politou, A.S., Kelly, G., Pastore, A., Temussi, P.A.: Protein stability in nanocages: a novel approach for influencing protein stability by molecular confinement. Journal of Molecular Biology 336, 203–212 (2004)
Eggers, D.K., Valentine, J.S.: Molecular confinement influences protein structure and enhances thermal stability. Protein Science 10, 250–261 (2001)
Lei, C., Shin, Y., Liu, J., Ackerman, E.J.: Synergetic effects of nanoporous support and urea on enzyme activity. Nano Letters 7, 1050–1053 (2007)
Lei, C., Soares, T.A., Shin, Y., Liu, J., Ackerman, E.J.: Enzyme specific activity in functionalized nanoporous supports Nanotechnology, vol. 19, pp. 125102–125111 (2008)
Lucent, D., Vishal, V., Pande, V.S.: Protein folding under confinement: A role for solvent. Proceedings of the National Academy of Sciences USA 104, 10430–10434 (2007)
Minton, A.P.: The influence of macromolecular crowding on HIV-1 protease internal dynamics. Proceedings of the National Academy of Sciences USA 276, 10577–10580 (2001)
Thurmalai, D., Klimov, D.K., Lorimer, G.H.: Caging helps proteins fold. Proceedings of the National Academy of Sciences USA 100, 11195–11197 (2003)
Zhou, H.X., Dill, K.A.: Stabilization of proteins in confined spaces. Biochemistry 40, 11289–11293 (2001)
Klimov, D.K., Newfield, D., Thirumalai, D.: Simulations of beta-hairpin folding spherical pores using distributed computing. Proceedings of the National Academy of Sciences USA 99, 8019–8024 (2002)
Takagi, F., Koga, N., Takada, S.: How protein thermodynamics and folding mechanisms are altered by the chaperonin cage: Molecular simulations. Proceedings of the National Academy of Sciences USA 100, 11367–11372 (2003)
Lu, D., Liu, Z., Wu, J.: Structural transitions of confined model proteins: molecular dynamics simulation and experimental validation. Biophysical Journal 90, 3224–3238 (2006)
Rathore, N., Knotts-IV, T.A., de Pablo, J.J.: Confinement effects on the thermodynamics of protein folding: Monte Carlo simulations. Biophysical Journal 90, 1767–1773 (2006)
Soares, T.A., Osman, M., Straatsma, T.P.: Molecular dynamics of organophosphorous hydrolases bound to the nerve agent soman. Journal of Chemical Theory and Computation 3, 1569–1579 (2007)
Benning, M.M., Hong, S.B., Raushel, F.M., Holden, H.M.: The binding of substrate analogs to phosphotriesterase. Journal of Biological Chemistry 275, 30556–30560 (2000)
Cornell, W.D., Cieplak, P., Bayly, C.I., Gould, I.R., Merz, K.M., Ferguson, D.M., Spellmeyer, D.C., Fox, T., Caldwell, W., Kollman, P.A.: A second generation force field for the simulation of proteins and nucleic acids. Journal of the American Chemical Society 117, 5179–5197 (1995)
Baker, N.A., Sept, D., Joseph, S., Holst, M.J., McCammon, J.A.: Electrostatics of nanosystems: application to microtubules and the ribosome. Proceedings of the National Academy of Sciences USA 98, 10037–10041 (2001)
Mustata, G.I., Soares, T.A., Briggs, J.M.: Molecular dynamics studies of alanine racemase: A structural model for drug design. Biopolymers 70, 186–200 (2003)
Soares, T.A., Lins, R.D., Straatsma, T.P., Briggs, J.M.: Internal dynamics and ionization states of the macrophage migration inhibitory factor: Comparison between wild-type and mutant forms. Biopolymers 65, 313–323 (2002)
Bylaska, E.J., Jong, W.A.d., Kowalski, K., Straatsma, T.P., Valiev, M., Wang, D., Aprà, E., Windus, T.L., Hirata, S., Hackler, M.T., Zhao, Y., Fan, P.-D., Harrison, R.J., Dupuis, M., Smith, D.M.A., Nieplocha, J., Tipparaju, V., Krishnan, M., Auer, A.A., Nooijen, M., Brown, E., Cisneros, G., Fann, G.I., Frücht, H., Garza, J., Hirao, K., Kendall, R., Nichols, J.A., Tsemekhman, K., Wolinsk, K., Anchell, J., Bernholdt, D., Borowski, P., Clark, T., Clerc, D., Dachsel, H., Deegan, M., Dyall, K., Elwood, D., Glendening, E., Gutowski, M., Hess, A., Jaffe, J., Johnson, B., Ju, J., Kobayashi, R., Kutteh, R., Lin, Z., Littlefield, R., Long, X., Meng, B., Nakajima, T., Niu, S., Pollack, L., Rosing, M., Sandrone, G., Stave, M., Taylor, H., Thomas, G., Lenthe, J.v., Wong, A., Zhang, Z.: NWChem, A Computational Chemistry Package for Parallel Computers, Version 5.0. Pacific Northwest National Laboratory, Richland, Washington 99352-0999, USA (A modified version) (2006)
Lindahl, E., Hess, B., Spoel, D.v.d.: GROMACS 3.0: A package for molecular simulation and trajectory analysis. Journal of Molecular Modeling 7, 306–317 (2001)
García, A.E.: Large-amplitude nonlinear motions in proteins. Physical Review Letters 68, 2696–2699 (1992)
Boehr, D.D., Dyson, H.J., Wright, P.E.: An NMR Perspective on Enzyme Dynamics. Chemical Reviews 106, 3055–3079 (2006)
Whitten, S.T., Garcia-Moreno, E.B., Hilser, V.J.: Local conformational fluctuations can modulate the coupling between proton binding and global structural transitions in proteins. Proceedings of the National Academy of Sciences USA 102, 4282–4287 (2005)
Author information
Authors and Affiliations
Editor information
Rights and permissions
Copyright information
© 2008 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Gomes, D.E.B., Lins, R.D., Pascutti, P.G., Straatsma, T.P., Soares, T.A. (2008). Molecular Models to Emulate Confinement Effects on the Internal Dynamics of Organophosphorous Hydrolase. In: Bazzan, A.L.C., Craven, M., Martins, N.F. (eds) Advances in Bioinformatics and Computational Biology. BSB 2008. Lecture Notes in Computer Science(), vol 5167. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-85557-6_7
Download citation
DOI: https://doi.org/10.1007/978-3-540-85557-6_7
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-85556-9
Online ISBN: 978-3-540-85557-6
eBook Packages: Computer ScienceComputer Science (R0)