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Molecular Dynamics Computer Modelling and Protein Engineering

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Molecular Aspects of Biotechnology: Computational Models and Theories

Part of the book series: NATO ASI Series ((ASIC,volume 368))

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Abstract

A set of molecular dynamics computer simulation studies applied in protein design is reviewed. The picture begins to emerge that with present day force fields and molecular dynamics simulation techniques the essentials of proteins’ structural and dynamical features around their native states may be obtained. The perspective of computer simulation as a tool in molecular engineering is explored. We discuss modelling of collective motion in proteins’ secondary structural elements, thermal stability of protein structures, differential stability in protein folds and surface plasticity properties of proteins. Properties of the following proteins are touched: the carboxy terminal fragment of the L7/L12 ribosomal protein from Escherichia coli, the potato carboxypeptidase A protein inhibitor, bacteriophage T4 glutaredoxin and the retinol binding protein. Appended are discussions of the chemical mechanism of hydride transfer in horse liver alcohol dehydrogenase, the fundamentals of interactive dynamical computer graphics analysis and a survey of the theoretical framework of molecular dynamics simulations.

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References

  • Alber, T. (1989) ‘Mutational effects on protein stability’, Annu. Rev. Biochem., 58, 765–798.

    Article  CAS  Google Scholar 

  • Alber, T., Bell, J. A., Dao-Pin, S., Nicholson, H., Wozniak, J. A., Cook, S. & Matthews, B. W. (1988) ‘Replacements of Pro-86 in phage T4 lysozyme extend an a-helix but do not alter protein stability’, Science, 239, 631–635.

    Article  CAS  Google Scholar 

  • Alber, T., Dao-Pin, S., Wilson, K., Wozniak, J. A., Cook, S. P. & Matthews, B. W. (1987) ‘Contributions of hydrogen bonds of Thr-157 to the thermodynamic stability of phage T4 lysozyme’, Nature, 330, 41–46.

    Article  CAS  Google Scholar 

  • Anfmsen, C. B. (1973) ‘Principles that govern the folding of protein chains’, Science, 181, 223–230.

    Article  Google Scholar 

  • Borden, K. L. B. & Richards, F. M. (1990) ‘Folding kinetics of phage T4 thioredoxin’, Biochemistry, 29, 3071–3077.

    Article  CAS  Google Scholar 

  • Bowie, J. V., Reidhaar-Olson, J. F., Lim, W. A. & Sauer, R. T. (1990) ‘Deciphering the message in protein sequences: Tolerance to amino acid substitutions’, Science, 247, 1306–1310.

    Article  CAS  Google Scholar 

  • Brooks III, C. L., Karplus, M. & Pettit, B. M. (1988) ‘Proteins: A theoretical perspective of dynamics, Structure, and thermodynamics’, Adv. Chem. Phys., 71, 1–259.

    Article  Google Scholar 

  • Brünger, A. T. & Karplus, M. (1991) ‘Molecular dynamics simulations with experimental restraints’, Accounts of Chemical Research, 24, 54–61.

    Article  Google Scholar 

  • Bushuev, V. N., Gudkov, A. T., Liljas, A. & Sepetov, N. F. (1989) ‘The flexible region of protein L12 from bacterial ribosomes studied by proton nuclear magnetic resonance’, J. Biol. Chem., 264, 4498–4505.

    CAS  Google Scholar 

  • Carson, M. (1987) ‘Ribbon models of macromolecules’, J. Mol. Graph., 5, 103–106.

    Article  CAS  Google Scholar 

  • Chothia, C. & Lesk, A. (1986) ‘The relation between the divergence of sequence and structure in proteins’, EMBO J., 5, 823–826.

    CAS  Google Scholar 

  • Clore, G. M., Gronenbom, A. M., Nilges, M. & Ryan, C. A. (1987) ‘Three-dimensional structure of potato carboxypeptidase inhibitor in solution. A study using nuclear magnetic resonance, distance geometry, and restrained molecular dynamics.’, Biochemistry, 26, 8012–8023.

    Article  CAS  Google Scholar 

  • Creighton, T. E. (1983) ‘Secondary Structure’ in Proteins. Structures and molecular properties, W.R. Freeman and Company, New York, USA., pp. 235.

    Google Scholar 

  • Donner, D., Villems, R., Liljas, A. & Kurland, C. G. (1978) ‘Guanosinetriphosphatase activity dependent on elongation factor Tu and ribosomal protein L7/L12’, Proc. Natl. Acad. Sci. USA, 75, 3192–3195.

    Article  CAS  Google Scholar 

  • Drummond, M. L. J. (1988) ‘A supertensor formalism for solute-continuum solvent interactions with arbitrarily shaped cavity. II. Preliminary apllication to model systems’, J. Chem. Phys., 88, 5021–5026.

    Article  CAS  Google Scholar 

  • Efimov, A. V. (1984) ‘A novel super-secondary structure of proteins and the relation between the structure and the amino acid sequence’, PEBS Lett., 166, 33–38.

    CAS  Google Scholar 

  • Eklund, R., Cambillau, C., Sjöberg, B.-M., Holmgren, A., Jörnvall, H., Röög, J.-O. & Bränden, C.-I. (1984)’ Conformational and functional similarities between glutaredoxin and thioredoxins’, EMBO J., 3, 1443–1449.

    CAS  Google Scholar 

  • Eklund, H., Ingelman, M., Söderberg, B.-O., Ulin, T., Nordlund, P., Nikkola, M. & Joelsson, T. (1991) ‘The structure of oxidized bacteriophage T4 glutaredoxin (thioredoxin),’ submitted.

    Google Scholar 

  • Goto, Y., Calcaiano, L. I. & Fink, A. L. (1990a) ‘Acid-induced folding of proteins’, Proc. Natl. Acad. Sci. USA, 87, 573–577.

    Article  CAS  Google Scholar 

  • Goto, Y., Takahashi, N. & Fink, A. L. (1990b) ‘Mechanism of acid-induced folding of proteins’, Biochemistry, 29, 3480–3488.

    Article  CAS  Google Scholar 

  • Gudkov, A. T., Gongadze, G. M., Bushuev, V. N. & Okon, M. S. (1982) ‘Proton nuclear magnetic resonance study of the ribosomal protein L7/L12 in situ’, PEBS Lett., 138, 229–232.

    CAS  Google Scholar 

  • Hass, G. M., Ako, R., Grahn, D. T. & Neurath, H. (1976) ‘Carboxypeptidase inhibitor from potatoes. The effects of chemical modifications on inhibitory activity’, Biochemistry, 15, 93–100.

    Article  CAS  Google Scholar 

  • Hass, G. M. & Ryan, C. A. (1982) ‘Carboxypeptidase inhibitor from potatoes’, Meth. Enzymol., 80, 778–791.

    Article  Google Scholar 

  • Hermann, R. B. (1972) ‘Theory of hydrophobic bonding. II. The correlation of hydrocarbon solubility in water with solvent cavity surface area’, J. Phys. Chem., 76, 2754–2759.

    Article  CAS  Google Scholar 

  • Horjales, E., Aqvist, J., Leijonmarck, M. & Tapia, O. (1987) ‘Aspects of model building applied to the C-terminal domain of the L7/L12 protein from chloroplast ribosomes: A molecular dynamics study’, Biochem. Biophys. Res. Commun., 148, 954–961.

    Article  CAS  Google Scholar 

  • Joelson, T., Sjöberg, B.,-M. & Eklund, H. (1990) ‘Modifications of the active center of T4 thioredoxin by site-directed mutagenesis’, I. Biol. Chem., 265, 3183–3188.

    CAS  Google Scholar 

  • Karplus, M. & Petsko, G. A. (1990) ‘Molecular dynamics simulations in biology’, Nature, 347, 631–639.

    Article  CAS  Google Scholar 

  • Knowles, J. R. (1987) ‘Tinkering with enzymes: What are we learning?’, Science, 236, 1252–1258.

    Article  CAS  Google Scholar 

  • Kotler, M., Katz, R. A., Danho, W., Leis, J. & Skalka, A. M. (1988) ‘Synthetic peptides as substrates and inhibitors of a retroviral protease’, Proc. Natl. Acad. Sci. USA, 85, 4185–4189.

    Article  CAS  Google Scholar 

  • Kraut, J. (1988) ‘How do enzyme work?’, Science, 242, 533–540.

    Article  CAS  Google Scholar 

  • Kubo, R. (1959) ‘Lectures in theoretical physics’ in Brittin, W. E. & Dunham, L. G. (eds.), Interscience, London, UK,pp. 120.

    Google Scholar 

  • Lee, B. & Richards, F. M. (1971) “The interpretation of protein structures: Estimation of static accessibility’, J. Mol. Biol., 55, 379–400.

    Article  CAS  Google Scholar 

  • Leijonmarck, M. & Liljas, A. (1987) ‘Structure of the C-terminal domain of the ribosomal protein L7/L12 from Escherichia coli at 1.7Å’, J. Mol. Biol., 195, 555–580.

    Article  CAS  Google Scholar 

  • Lerner, R. L. & Tramontano, A. (1987) ‘Antibodies as enzymes’, TIBS, 12, 427–430.

    CAS  Google Scholar 

  • Lesk, A. M. & Chothia, C. (1980) ‘How different amino acid sequences determine similar protein structures: The structure and evolutionary dynamics of the globins’, J. Mol. Biol., 136, 225–270.

    Article  CAS  Google Scholar 

  • Levitt, M. (1978) ‘Conformational preferences of amino acids in globular proteins’, Biochemistry, 17, 4277–4285.

    Article  CAS  Google Scholar 

  • Liljas, A. (1982) ‘Structural studies of ribosomes’, Prog. Biophys. Molec. Biol., 40, 161–228.

    Article  CAS  Google Scholar 

  • Makinen, M. W., Troyer, J. M., van der Werff, H., Berendsen, H. J. C. & van Gunsteren, W. F. (1989) ‘Dynamical structure of carboxypeptidase A’, J. Mol. Biol., 207, 201–216.

    Article  CAS  Google Scholar 

  • Marquis, D. M. & Fahnestock, S. R. (1978) ‘A complex of acidic ribosomal proteins. Evidence of a four-to-one complex of proteins in the Bacillus stearothermophilus ribosome’, J. Mol. Biol., 119, 557–567.

    Article  CAS  Google Scholar 

  • Marquis, D. M. & Fahnestock, S. R. (1980) ‘Stoichiometry and structure of a complex of acidic ribosomal proteins’, J. Mol. Biol., 142, 161–179.

    Article  CAS  Google Scholar 

  • Marquis, D. M., Fahnestock, S. R., Henderson, E., Woo, D., Schwinge, S., Clark, M. W. & Lake, J. A. (1981)’ The L7/L12 stalk, a conserved feature of the prokariotic ribosome, is attached to the large subunit through its N-terminus’, J. Mol. Biol., 150, 121–132.

    Article  CAS  Google Scholar 

  • McCammon, J. A. & Harvey, S. C. (1987) Dynamics of proteins and nucleic acids, Cambridge University Press, Cambridge, UK.

    Google Scholar 

  • Meyer, A. (1986) ‘The size of molecules’, Chem. Soc. Rev., 15, 449–474.

    Article  CAS  Google Scholar 

  • Navia, M. A., Fitzgerald, P. M. D., McKeever, B. M., Leu, C.-T., Heimbach, J. C., Herber, W. K., Sigal, I. S., Darke, P. L. & Springer, J. P. (1989a) ‘Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-I’, Nature, 337, 615–620.

    Article  CAS  Google Scholar 

  • Navia, M. A., McKeever, B. M., Springer, J. P., Lin, T. Y., Williams, H. R., Fluder, E. M., Dom, C. P. & Hoogsteen, K. (1989b) ‘Structure of human neutrophil elastase in complex with peptide chloromethyl ketone inhibitor at 1.84Å resolution’, Proc. Natl. Acad. Sci. USA, 86, 7–11.

    Article  CAS  Google Scholar 

  • Nilsson, O. (1990) ‘Molecular conformational space analysis using computer graphics: Going beyond FRODO’, J. Mol. Graph., 8, 192–200.

    Article  CAS  Google Scholar 

  • Nilsson, O. & Tapia, O. (1991) ‘Electrostatic forces and the structural stability of a modelled bacteriophage T4 glutaredoxin fold: Molecular dynamics simulations of polyglycine 87-mers’, J. Mol. Struct. (Theochem), in press.

    Google Scholar 

  • Nilsson, O., Tapia, O. & van Gunsteren, W. F. (1990)’ Structure and fluctuations of bacteriophage T4 glutaredoxin modelled by molecular dynamics’, Biochem. Biophys. Res. Commun., 171, 581–588.

    Article  CAS  Google Scholar 

  • Oliva, B., Nilsson, O., Wlistlund, M., Cardenas, R., Querol, E., Avilés, F. X. & Tapia, O. (1991a) ‘A molecular dynamics study of a model built Pro-36-Gly mutant derived from the potato carboxypeptidase A inhibitor protein’, Biochem. Biophys. Res. Commun., 176, 627–632.

    Article  CAS  Google Scholar 

  • Oliva, B., Wlistlund, M., Nilsson, O., Cardenas, R., Querol, E., Avilés, F. X. & Tapia, O. (1991b) ‘Stability and fluctuations of the carboxypeptidase A protein inhibitor fold: A molecular dynamics study’, Biochem. Biophys. Res. Commun., 176, 616–621.

    Article  CAS  Google Scholar 

  • Pascual-Ahuir, J. L. & Silla, E. (1989) ‘Gepol: A method to calculate the envelope surface. Computations of changes in conformational area and volume of n-octanol’ in Carbó, R. (ed.), Quantum chemistry-Basic aspects, actual trends, Elsevier Scientific Publishers B.V., Amsterdam, The Netherlands, pp. 597–603.

    Google Scholar 

  • Pascual-Ahuir, J. L., Silla, E., Tomasi, J. & Bonacorsi, R. (1987) ‘Electrostatic interaction of solute with a continuum. Improved description of the cavity and of the surface cavity bound charge distribution’, J. Comput. Chem., 8, 778–787.

    Article  CAS  Google Scholar 

  • Rees, D. C. & Lipscomb, W. N. (1982) ‘Refined crystal structure of the potato inhibitor complex of carboxypeptidase A at 2.5Å resolution’, J. Mol. Biol., 160, 475–498.

    Article  CAS  Google Scholar 

  • Reidhaar-Olsen, J. F. & Sauer, R. T. (1990) ‘Functionally acceptable substitutions in two α-helical regions of λ repressor’, Proteins, 7, 306–316.

    Article  Google Scholar 

  • Richards, F. M. (1977) ‘Areas, volumes, packing and protein structure’, Annu. Rev. Biophys. Bioeng., 6

    Google Scholar 

  • Rossman, M. G. & Moras, D. (1974) ‘Chemical and biological evolution of a nucleotide-binding protein’, Nature, 250, 194–199.

    Article  Google Scholar 

  • Schnebli, H. P. & Braun, N. J. (1986) ‘Proteinase inhibitors as drugs’ in Salvesen & Barret (eds.), Proteinase Inhibitors, Elsevier Science Publishers BV, Amsterdam, pp. 613–627.

    Google Scholar 

  • Silla, E., Villar, F., Nilsson, O., Pascual-Ahuir, J. L. & Tapia, O. (1990) ‘Molecular volumes and surfaces of biomacromolecules via GEPOL: A fast and efficient algorithm’, J. Mol. Graph., 8, 168–172.

    Article  CAS  Google Scholar 

  • Skolnick, J. & Kolinski, A. (1990) ‘Simulations of the folding of a globular protein’, Science, 250, 1121–1125.

    Article  CAS  Google Scholar 

  • Soares, C., Nilsson, O. & Tapia, O., unpublished results.

    Google Scholar 

  • Söderberg, B.-O., Sjöberg, B.-M., Sonnerstam, U. & Brändén, C.-I. (1978) ‘Three-dimensional structure of thioredoxin induced by bacteriophage T4’, Proc. Natl. Acad. Sci. USA, 75, 5827–5830.

    Article  Google Scholar 

  • Tanford, C. (1968) ‘Protein denaturation’, Adv. Prot. Chem., 23, 121–282.

    Article  CAS  Google Scholar 

  • Tapia, O. (1991) ‘Theory of solvent effects and chemical reactions’, Rep. Mol. Th., in press.

    Google Scholar 

  • Tapia, O., Cardenas, R., Andres, J., Krechl, J., Campillo, M. & Colonna-Cesari, F. (1991) ‘Electronic aspects of LADH catalytic mechanism’, Int. J. Quantum. Chem., 39, 767–786.

    Article  CAS  Google Scholar 

  • Tapia, O., Nilsson, O., Campillo, M., Aqvist, J. & Horjales, E. (1990) ‘Low frequency motions in protein’s secondary structures. Molecular dynamics studies on carboxy terminal fragment of L7/L12 ribosomal protein’ in Sarma, R. H. & Sarma, M. H. (eds.), Structure & Methods, DNA Protein Complexes., Adenine Press, New York, USA, pp. 147–170.

    Google Scholar 

  • Tapia. O., Oliva, B., Nilsson, O., Querol, E. & Avilés, F. X. (1991) ‘Molecular dynamics simulation as a tool to design mutant proteins: Comparative studies of the modelled potato carboxypeptidase A inhibitor and its Pro-36’Gly mutant with the receptor-docked X-ray structure’ in Giralt, E. & Andreu, D. (eds.), Peptides 1990, ESCOM Science Publishers B.V., Leiden, The Netherlands, pp. 581-584.

    Google Scholar 

  • Tapia, O. & Aqvist, J. (1989) ‘Molecular dynamics as a tool for structural and functional predications: The retinol binding and chloroplast C-terminal fragment of the L7/L12 ribosomal protein’, Prog. Clin. Biol. Res., 289, 55–64.

    CAS  Google Scholar 

  • van Gunsteren, W. F. (1988) ‘The role of computer simulations techniques in protein engineering’, Protein Engineering, 2, 5–13.

    Article  Google Scholar 

  • van Gunsteren, W. F. & Berendsen, H. J. C. (1990) ‘Computer simulation of molecular dynamics: Methodology, applications, and perspectives in chemistry’, Angewandte Chemie, 29, 992–1023.

    Article  Google Scholar 

  • Weiner, P. K. & Kollman, P. A. (1981) ‘AMBER: Assisted model building with energy refinement. A general program for modeling molecules and their interactions’, J. Comput Chem., 2, 287–303.

    Article  CAS  Google Scholar 

  • Weiner, S. J., Kollman, P. A., Case, D. A., Singh, U. C., Ghio, C., Alagona, G., Profeta, S. & Weiner, P. (1984) ‘A new force field for molecular mechanical simulation of nucleic acids and proteins’, J. Am. Chem. Soc., 106, 765–784.

    Article  CAS  Google Scholar 

  • Åqvist, J., Leijonmarck, M. & Tapia. O. (1989) ‘A molecular dynamics study of the C-terminal fragment of the L7/L12 ribosomal protein’, Eur. Biophys. J., 16, 327–339.

    Article  Google Scholar 

  • Åqvist, J., Sandbolm, P., Jones, T. A., Newcomer, M. E., van Gunsteren, W. F. & Tapia, O. (1986) ‘Molecular dynamics simulation of the holo and apo forms of the retinol binding protein. Structural and dynamical changes induced by retinol removal’, J. Mol. Biol., 192, 593–604.

    Article  Google Scholar 

  • Åqvist, J. & Tapia, O. (1987) ‘Surface fractality as a guide for studying protein-protein interactions’, J. Mol. Graph., 5, 30–34.

    Article  Google Scholar 

  • Åqvist, J., van Gunsteren, W. F., Leijonmarck, M. & Tapia, O. (1985)’ A molecular dynamics study of the C-terminal fragment of the L7/L12 ribosomal protein. Secondary structure motion in a 150 picosecond trajectory’, J. Mol. Biol., 83, 461–477.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Physical Chemistry, University of Uppsala, Box 532, S-751 21, Uppsala, Sweden

    O. Tapia & O. Nilsson

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  1. O. Tapia
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  2. O. Nilsson
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  1. Department of Chemistry, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain

    Juan Bertrán

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© 1992 Kluwer Academic Publishers

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Tapia, O., Nilsson, O. (1992). Molecular Dynamics Computer Modelling and Protein Engineering. In: Bertrán, J. (eds) Molecular Aspects of Biotechnology: Computational Models and Theories. NATO ASI Series, vol 368. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-2538-3_6

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  • DOI: https://doi.org/10.1007/978-94-011-2538-3_6

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-0-7923-1728-9

  • Online ISBN: 978-94-011-2538-3

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