Advertisement

Steered Molecular Dynamics

  • Sergei Izrailev
  • Sergey Stepaniants
  • Barry Isralewitz
  • Dorina Kosztin
  • Hui Lu
  • Ferenc Molnar
  • Willy Wriggers
  • Klaus Schulten
Part of the Lecture Notes in Computational Science and Engineering book series (LNCSE, volume 4)

Abstract

Steered molecular dynamics (SMD) induces unbinding of ligands and conformational changes in biomolecules on time scales accessible to molecular dynamics simulations. Time-dependent external forces are applied to a system, and the responses of the system are analyzed. SMD has already provided important qualitative insights into biologically relevant problems, as demonstrated here for applications ranging from identification of ligand binding pathways to explanation of elastic properties of proteins. First attempts to deduce potentials of mean force by discounting irreversible work performed on the system are summarized. The non-equilibrium statistical mechanics underlying analysis of SMD data is outlined.

Keywords

Binding Pocket Thyroid Hormone Receptor Rupture Force Steer Molecular Dynamic Atomic Force Microscopy Experiment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [Ajay and Murcko, 1995]
    Ajay, and Murcko, M.: Computational methods to predict binding free energy in ligand-receptor complexes. J. Med. Chem. 38 (1995) 4953–4967CrossRefGoogle Scholar
  2. [Allen et al., 1996]
    Allen, P. G., Laham, L. E., Way, M., and Janmey, P. A.: Binding of phosphate, aluminum fluoride, or beryllium fluoride to F-actin inhibits severing by gelsolin. J. Biol. Chem. 271 (1996) 4665–4670CrossRefGoogle Scholar
  3. [Andersson et al., 1992]
    Andersson, M. L., Nordström, K., Demczuck, S., Harbers, M., and Vennström, B.: Thyroid hormone alters the DNA binding properties of chicken thyroid hormone receptors α and β. Nucl. Acids Res. 20 (1992) 4803–4810CrossRefGoogle Scholar
  4. [Baljon and Robbins, 1996]
    Baljon, R. C. A., and Robbins, M. O.: Energy dissipation during rupture of adhesive bonds. Science. 271 (1996) 482–484CrossRefGoogle Scholar
  5. [Baisera et al., 1997]
    Baisera, M., Stepaniants, S., Izrailev, S., Oono, Y., and Schulten, K.: Reconstructing potential energy functions from simulated force-induced unbinding processes. Biophys. J. 73 (1997) 1281–1287CrossRefGoogle Scholar
  6. [Baisera et al, 1996]
    Baisera, M. A., Wriggers, W., Oono, Y., and Schulten, K.: Principal component analysis and long time protein dynamics. J. Phys. Chem. 100 (1996) 2567–2572CrossRefGoogle Scholar
  7. [Bell, 1978]
    Bell, G. L: Models for the specific adhesion of cells to cells. Science. 200 (1978) 618–627CrossRefGoogle Scholar
  8. [Binning et al., 1986]
    Binning, G., Quate, C. F., and Gerber, G.: Atomic force microscope. Phys. Rev. Lett. 56 (1986) 930–933CrossRefGoogle Scholar
  9. [Block and Svoboda, 1994]
    Block, S., and Svoboda, K.: Biological applications of optical forces. Ann. Rev. Biophys. Biomol. Struct. 23 (1994) 247–285CrossRefGoogle Scholar
  10. [Booth et al, 1996]
    Booth, P. J., Farooq, A., and Flitsch, S. L.: Retinal binding during folding and assembly of the membrane protein bacteriorhodopsin. Biochemistry. 35 (1996) 5902–5909CrossRefGoogle Scholar
  11. [Brent et al, 1989]
    Brent, G. A., Dunn, M. K., Harney, J. W., Gulick, T., and Larsen, P. R.: Thyroid hormone aporeceptor represses T3 inducible promoters and blocks activity of the retinoic acid receptor. New Biol. 1 (1989) 329–336Google Scholar
  12. [Cevc and Marsh, 1987]
    Cevc, G., and Marsh, D.: Phospholipid Bilayers: Physical Principles and Models. John Wiley & Sons, New York, 1987.Google Scholar
  13. [Chang et aL, 1988]
    Chang, C.-H., Jonas, R., Govindjee, R., and Ebrey, T.: Regeneration of blue and purple membranes for deionized bleached membranes of halobacterium halobium. Photochem. Photobiol. 47 (1988) 261–265CrossRefGoogle Scholar
  14. [Chilcotti et al, 1995]
    Chilcotti, A., Boland, T., Ratner, B. D., and Stayton, P. S.: The relationship between ligand-binding thermodynamics and protein-ligand interaction forces measured by atomic force microscopy. Biophys. J. 69 (1995) 2125–2130CrossRefGoogle Scholar
  15. [Cohen et al, 1990]
    Cohen, N., Blaney, J., Humblet, C., Gund, P., and Barry, D.: Molecular modeling software and methods for medicinal chemistry. J. Med. Chem. 33 (1990) 883–894CrossRefGoogle Scholar
  16. [Colman, 1994]
    Colman, P.: Structure-based drug design. Curr. Opinion Struct. Biol. 4 (1994) 868–874CrossRefGoogle Scholar
  17. [Damm et al., 1989]
    Damm, K., Thompson, C. C., and Evans, R. M.: Protein encoded by v-erbA functions as a thyroid-hormone receptor antagonist. Nature. 339 (1989) 593–597CrossRefGoogle Scholar
  18. [Dancker and Hess, 1990]
    Dancker, P., and Hess, L.: Phalloidin reduces the release of inorganic phosphate during actin polymerization. Biochim. Biophys. Acta. 1035 (1990) 197–200CrossRefGoogle Scholar
  19. [Dennis, 1983]
    Dennis, E. A.: Phospholipases. In The enzymes vol. XVI, 1983.Google Scholar
  20. [Devreotes and Zigmond, 1988]
    Devreotes, P. N., and Zigmond, S. H.: Chemotaxis in eukaryotic cells: a focus on leukocytes and Dictyostelium. Ann. Rev. Cell Biol. 4 (1988) 649–686CrossRefGoogle Scholar
  21. [Eaton et al., 1997]
    Eaton, W. A., Munos, V., Thompson, P. A., Chan, C.-K., and Hofrichter, J.: Submillisecond kinetics of protein folding. Curr. Opinion Struct. Biol. 7 (1997) 10–14CrossRefGoogle Scholar
  22. [Elber, 1996]
    Elber, R.: Reaction path studies of biological molecules. In Recent developments in theoretical studies of proteins (Advanced series in physical chemistry, Vol. 7). R. Elber, editor. World Scientific, Singapore, 1996.Google Scholar
  23. [Evans et al., 1991]
    Evans, E., Berk, D., and Leung, A.: Detachment of agglutininbonded red blood cells. Biophys. J. 59 (1991) 838–848CrossRefGoogle Scholar
  24. [Evans et aL, 1995]
    Evans, E., Ritchie, K., and Merkel, R.: Sensitive force technique to probe molecular adhesion and structural linkages at biological interfaces. Biophys. J. 68 (1995) 2580–2587CrossRefGoogle Scholar
  25. [Evans and Ritchie, 1997]
    Evans, E., and Ritchie, K.: Dynamic strength of molecular adhesion bonds. Biophys. J. 72 (1997) 1541–1555CrossRefGoogle Scholar
  26. [Florin et al, 1994]
    Florin, E.-L., Moy, V. T., and Gaub, H. E.: Adhesion force between individual ligand-receptor pairs. Science. 264 (1994) 415–417CrossRefGoogle Scholar
  27. [Gardiner, 1985]
    Gardiner, C. W.: Handbook of Stochastic Methods for Physics, Chemistry, and the Natural Sciences. Springer-Verlag, New York, 1985.Google Scholar
  28. [Gilson et al, 1997]
    Gilson, M., Given, J., Bush, B., and McCammon, J.: The statistical-thermodynamic basis for computation of binding affinities: A critical review. Biophys. J. 72 (1997) 1047–1069CrossRefGoogle Scholar
  29. [Green, 1975]
    Green, N. M.: Avidin. Advan. Prot. Chem. 29 (1975) 85–133CrossRefGoogle Scholar
  30. [Grubmüller, 1995]
    Grubmüller, H.: Predicting slow structural transitions in macromolecular systems: Conformational Flooding. Phys. Rev. E. 52 (1995) 2893–2906CrossRefGoogle Scholar
  31. [Grubmüller et al., 1996]
    Grubmüller, H., Heymann, B., and Tavan, P.: Ligand binding and molecular mechanics calculation of the streptavidin-biotin rupture force. Science. 271 (1996) 997–999CrossRefGoogle Scholar
  32. [Hanessian and Devasthale, 1996]
    Hanessian, S., and Devasthale, P.: Design and synthesis of novel, pseudo C2 symmetric inhibitors of HIV protease. Bioorg. Med. Chem. Lett. 6 (1996) 2201–2206CrossRefGoogle Scholar
  33. [Humphrey et al., 1996]
    Humphrey, W. F., Dalke, A., and Schulten, K.: VMD-Visual Molecular Dynamics. J. Mol. Graphics. 14 (1996) 33–38CrossRefGoogle Scholar
  34. [Improta et aL, 1996]
    Improta, S., Politou, A., and Pastore, A.: Immunoglobulinlike modules from titin I-band: extensible components of muscle elasticity. Structure. 4 (1996) 323–337CrossRefGoogle Scholar
  35. [Israelachvili, 1992]
    Israelachvili, J. N.: Intermolecular and Surface Forces. Academic Press, London, 1992.Google Scholar
  36. [Isralewitz et al., 1997]
    Isralewitz, B., Izrailev, S., and Schulten, K.: Binding pathway of retinal to bacterio-opsin: A prediction by molecular dynamics simulations. Biophys. J. 73 (1997) 2972–2979CrossRefGoogle Scholar
  37. [Izrailev et aL, 1997]
    Izrailev, S., Stepaniants, S., Baisera, M., Oono, Y., and Schulten, K.: Molecular dynamics study of unbinding of the avidin-biotin complex. Biophys. J. 72 (1997) 1568–1581CrossRefGoogle Scholar
  38. [Jain et aL, 1995]
    Jain, M. K., Gelb, M., Rogers, J., and Berg, O.: Kinetic basis for interfacial catalysis by phospholipase A2. Methods in enzymology. 249 (1995) 567–614CrossRefGoogle Scholar
  39. [Jarzynski, 1997a]
    Jarzynski, C: Equilibrium free-energy differences from nonequilibrium measurements: A master equation approach. Phys. Rev. E. 56 (1997a) 5018–5035CrossRefGoogle Scholar
  40. [Jarzynski, 1997b]
    Jarzynski, C: Nonequilibrium equality for free energy differences. Phys. Rev. Lett. 78 (1997b) 2690–2693CrossRefGoogle Scholar
  41. [Kellermayer et al., 1997]
    Kellermayer, M., Smith, S., Granzier, H., and Bustamante, C: Folding-unfolding transition in single titin modules characterized with laser tweezers. Science. 276 (1997) 1112–1116CrossRefGoogle Scholar
  42. [Kumar et al., 1992]
    Kumar, S., Bouzida, D., Swendsen, R. H., Kolman, P. A., and Rosenberg, J. M.: The weighted histogram analysis method for free-energy calculations on biomolecules. I. The method. J. Comp. Chem. 13 (1992) 1011–1021CrossRefGoogle Scholar
  43. [Labeit et al., 1997]
    Labeit, S., Kolmerer, B., and Linke, W.: The giant protein titin: emerging roles in physiology and pathophysiology. Circulation Research. 80 (1997) 290–294CrossRefGoogle Scholar
  44. [Lebon et al., 1996]
    Lebon, F., Vinals, C., Feytmans, E., and Durant, F.: Computational drug design of new HIV-1 protease inhibitors. Arch. Phys. Biochem. 104 (1996) B44.Google Scholar
  45. [Leckband et al, 1994]
    Leckband, D. E., Schmitt, F. J., Israelachvili, J. N., and Knoll, W.: Direct force measurements of specific and nonspecific protein interactions. Biochemistry. 33 (1994) 4611–4624CrossRefGoogle Scholar
  46. [Lu et al., 1998]
    Lu, H., Isralewitz, B., Krammer, A., Vogel, V., and Schulten, K.: Unfolding of titin immunoglobulin domains by steered molecular dynamics simulation. Biophys. J. 75 (1998) 662–671CrossRefGoogle Scholar
  47. [Lüdemann et al., 1997]
    Lüdemann, S. K., Carugo, O., and Wade, R. C.: Substrate access to cytochrome P450cam: A comparison of a thermal motion pathway analysis with molecular dynamics simulation data. J. Mol. Model. 3 (1997) 369–374CrossRefGoogle Scholar
  48. [Marrink et al., 1998]
    Marrink, S.-J., Berger, O., Tieleman, P., and Jähnig, F.: Adhesion forces of lipids in a phospholipid membrane studied by molecular dynamics dimulations. Biophys. J. 74 (1998) 931–943CrossRefGoogle Scholar
  49. [Marrone et al., 1997]
    Marrone, T., Briggs, J., and McCammon, J.: Structurebased drug design: Computational advances. Ann. Rev. Pharm. Tox. 37 (1997) 71–90CrossRefGoogle Scholar
  50. [Maruyama, 1997]
    Maruyama, K.: Connectin/titin, a giant elastic protein of muscle. FASEB J. 11 (1997) 341–345Google Scholar
  51. [McCammon and Harvey, 1987]
    McCammon, J. A., and Harvey, S. C: Dynamics of Proteins and Nucleic Acids. Cambridge University Press, Cambridge, 1987.CrossRefGoogle Scholar
  52. [Moy et al, 1994a]
    Moy, V. T., Florin, E.-L., and Gaub, H. E.: Adhesive forces between ligand and receptor measured by AFM. Colloids and Surfaces. 93 (1994a) 343–348CrossRefGoogle Scholar
  53. [Moy et al, 1994b]
    Moy, V. T., Florin, E.-L., and Gaub, H. E.: Intermolecular forces and energies between ligands and receptors. Science. 266 (1994b) 257–259CrossRefGoogle Scholar
  54. [Nadler and Schulten, 1984]
    Nadler, W., and Schulten, K.: Theory of Mössbauer spectra of proteins fluctuating between conformational substates. Proc. Natl. Acad. Sci. USA. 81 (1984) 5719–5723CrossRefGoogle Scholar
  55. [Nelson et al., 1995]
    Nelson, M., Humphrey, W., Gursoy, A., Dalke, A., Kalé, L., Skeel, R., Schulten, K., and Kufrin, R.: MDScope-A visual computing environment for structural biology. Comput. Phys. Commun. 91 (1995) 111–134CrossRefGoogle Scholar
  56. [Nelson et al., 1996]
    Nelson, M., Humphrey, W., Gursoy, A., Dalke, A., Kalé, L., Skeel, R. D., and Schulten, K.: NAMD-A parallel, object-oriented molecular dynamics program. J. Supercomputing App. 10 (1996) 251–268CrossRefGoogle Scholar
  57. [Oberhauser et al., 1998]
    Oberhauser, A. F., Marszalek, P. E., Erickson, H., and Fernandez, J.: The molecular elasticity of tenascin, an extracellular matrix protein. Nature. In Press.Google Scholar
  58. [Oesterhelt et al., 1992]
    Oesterhelt, D., Tittor, J., and Bamberg, E.: A unifying concept for ion translocation in retinal proteins. J. Bioenerg. Biomemb. 24 (1992) 181–191CrossRefGoogle Scholar
  59. [Oesterhelt and Schumann, 1974]
    Oesterhelt, D., and Schumann, L.: Reconstitution of bacteriorhodopsin. FEBS Lett. 44 (1974) 262–265CrossRefGoogle Scholar
  60. [Olender and Elber, 1996]
    Olender, R., and Elber, R.: Calculation of classical trajectories with a very large time step: Formalism and numerical examples. J. Chem. Phys. 105 (1996) 9299–9315CrossRefGoogle Scholar
  61. [Picot et al., 1994]
    Picot, D., Loll, P. J., and Garavito, M.: The X-ray crystal structure of the membrane protein prostaglandin H 2 synthase-1. Nature. 367 (1994) 243–249CrossRefGoogle Scholar
  62. [Pollard et al, 1992]
    Pollard, T. D., Goldberg, L, and Schwarz, W. H.: Nucleotide exchange, structure, and mechanical properties of filaments assembled from ATP-actin and ADP-actin. J. Biol. Chem. 267 (1992) 20339–20345Google Scholar
  63. [Resat et al., 1996]
    Resat, H., Mezei, M., and McCammon, J. A.: Use of the grand canonical ensemble in potential of mean force calculations. J. Phys. Chem. 100 (1996) 1426–1433CrossRefGoogle Scholar
  64. [Rief et al, 1997]
    Rief, M., Gautel, M., Oesterhelt, F., Fernandez, J. M., and Gaub, H. E.: Reversible unfolding of individual titin immunoglobulin domains by AFM. Science. 276 (1997) 1109–1112CrossRefGoogle Scholar
  65. [Schlitter et al., 1993]
    Schlitter, J., Engels, M., Krüger, P., Jacoby, E., and Wollmer, A.: Targeted molecular dynamics simulation of conformational change—application to the t ↔ r transition in insulin. Molecular Simulation. 10 (1993) 291–308CrossRefGoogle Scholar
  66. [Schulten et al., 1995]
    Schulten, K., Humphrey, W., Logunov, L, Sheves, M., and Xu, D.: Molecular dynamics studies of bacteriorhodopsin’s photocycles. Israel Journal of Chemistry. 35 (1995) 447–464Google Scholar
  67. [Slotboom et al, 1982]
    Slotboom, A. J., Verheij, H. M., and Haas, G. H. D.: On the mechanism of phospholipase A2. In Phospholipids, J. N. Hawthorne, and G. B. Ansell, editors. Elsevier Biomédical Press, New York. 359–435, 1982Google Scholar
  68. [Small, 1989]
    Small, J. V.: Microfilament-based motility in non-muscle cells. Curr. Opinion Cell Biol. 1 (1989) 75–79MathSciNetCrossRefGoogle Scholar
  69. [Smith and DeWitt, 1996]
    Smith, W., and DeWitt, D.: Prostaglandin endoperoxide H synthases-1 and-2. Adv. Immunol. 62 (1996) 167–215CrossRefGoogle Scholar
  70. [Stepaniants et al., 1997]
    Stepaniants, S., Izrailev, S., and Schulten, K.: Extraction of lipids from phospholipid membranes by steered molecular dynamics. J. Mol. Model. 3 (1997) 473–475CrossRefGoogle Scholar
  71. [Strynadka et al., 1996]
    Strynadka, N., Eisenstein, M., Katchalski-Katzir, E., Shoichet, B., Kuntz, L, Abagyan, R., Totrov, M., Janin, J., Cherfils, J., Zimmerman, F., Olson, A., Duncan, B., Rao, M., Jackson, R., Sternberg, M., and James, M.: Molecular docking programs successfully predict the binding of a β-lactamase inhibitory protein to TEM-1 β-lactamase. Nature Struct. Biol. 3 (1996) 233–239CrossRefGoogle Scholar
  72. [Thaisrivongs et al., 1996]
    Thaisrivongs, S., Romero, D., Tommasi, R., Janakiraman, M., Strohbach, J., Turner, S., Biles, C., Morge, R., Johnson, P., Aristoff, P., Tomich, P., Lynn, J., Horng, M., Chong, K., Hinshaw, R., Howe, W., Finzel, B., and Watenpaugh, K.: Structure-based design of HIV protease inhibitors-5,6-dihydro-4-hydroxy-2-pyrones as effective, nonpeptidic inhibitors. J. Med. Chem. 39 (1996) 4630–4642CrossRefGoogle Scholar
  73. [Theriot et al, 1992]
    Theriot, J. A., Mitchison, T. J., Tilney, L. G., and Portnoi, D. A.: The rate of act in-based motility of intracellular Listeria monocytogenes equals the rate of actin polymerization. Nature. 357 (1992) 257–260CrossRefGoogle Scholar
  74. [Tskhovrebova et al., 1997]
    Tskhovrebova, L., Trinick, J., Sleep, J., and Simmons, R.: Elasticity and unfolding of single molecules of the giant protein titin. Nature. 387 (1997) 308–312CrossRefGoogle Scholar
  75. [Wagner et al, 1995]
    Wagner, R., Apriletti, J. W., McGrath, M. E., West, B. L., Baxter, J. D., and Fletterick, R. J.: A structural role for hormone in the thyroid hormone receptor. Nature. 378 (1995) 690–697CrossRefGoogle Scholar
  76. [Wang et al., 1993]
    Wang, K., McCarter, R., Wright, J., Beverly, J., and Ramirez-Mitchell, R.: Viscoelasticity of the sarcomere matrix of skeletal muscles. Biophys. J. 64 (1993) 1161–1177CrossRefGoogle Scholar
  77. [Wriggers and Schulten, 1997a]
    Wriggers, W., and Schulten, K.: Protein domain movements: Detection of rigid domains and visualization of hinges in comparisons of atomic coordinates. Proteins: Struc. Func. and Genetics. 29 (1997a) 1–14CrossRefGoogle Scholar
  78. [Wriggers and Schulten, 1997b]
    Wriggers, W., and Schulten, K.: Stability and dynamics of G-actin: Back door water diffusion and behavior of a subdomain 3/4 loop. Biophys. J. 73 (1997b) 624–639CrossRefGoogle Scholar
  79. [Wriggers and Schulten, 1998]
    Wriggers, W., and Schulten, K.: Investigating a back door mechanism of actin phosphate release by steered molecular dynamics. Biophys. J. Submitted.Google Scholar
  80. [Xu et al., 1996]
    Xu, D., Phillips, J. C., and Schulten, K.: Protein response to external electric fields: Relaxation, hysteresis and echo. J. Phys. Chem. 100 (1996) 12108–12121CrossRefGoogle Scholar
  81. [Zhang and Hermans, 1996]
    Zhang, L., and Hermans, J.: Hydrophilicity of cavities in proteins. Proteins: Struc. Func. and Genetics. 24 (1996) 433–438CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • Sergei Izrailev
    • 1
  • Sergey Stepaniants
    • 1
  • Barry Isralewitz
    • 1
  • Dorina Kosztin
    • 1
  • Hui Lu
    • 1
  • Ferenc Molnar
    • 1
  • Willy Wriggers
    • 1
  • Klaus Schulten
    • 1
  1. 1.Beckman InstituteUniversity of Illinois at Urbana-ChampaignUrbanaUSA

Personalised recommendations