European Biophysics Journal

, Volume 24, Issue 3, pp 137–141 | Cite as

Orientational steering in enzyme-substrate association: Ionic strength dependence of hydrodynamic torque effects

  • Jan Antosiewicz
  • James M. Briggs
  • J. Andrew McCammon


The effect of hydrodynamic torques on the association rate constants for enzyme-ligand complexation is investigated by Brownian dynamics simulations. Our hydrodynamic models of the enzyme and ligand are composed of spherical elements with friction forces acting at their centers. A quantitative measure of hydrodynamic torque orientational effects is introduced by choosing, as a reference system, an enzyme-ligand model with the same average hydrodynamic interactions but without orientational dependence. Our simple models show a 15% increase in the rate constant caused by hydrodynamic torques at physiological ionic strength. For more realistic hydrodynamic models, which are not computationally feasible at present, this effect is probably higher. The most important finding of this work is that hydrodynamic complementarity in shape (i.e. like the fitting together of pieces of a puzzle) is most effective for interactions between molecules at physiological ionic strength.

Key words

Hydrodynamic torques Enzyme-substrate association Ionic strength dependence 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Allison SA, Srinivasan N, McCammon JA, Northrup SH (1984) Diffusioncontrolled reactions between a spherical target and dumbell dimer by brownian dynamics simulation. J Phys Chem 88:6152–6157Google Scholar
  2. Antosiewicz J, McCammon JA (1995) Electrostatic and hydrodynamic orientational steering effects in enzyme-substrate association. Biophys J 69:57–65Google Scholar
  3. Brune D, Kim S (1994) Hydrodynamic steering effects in protein association. Proc Natl Acad Sci USA 91:2930–2934Google Scholar
  4. Davis ME, McCammon JA (1990) Electrostatics in biomolecular structure and dynamics. Chem Rev 90:509–521Google Scholar
  5. Davis ME, Madura JD, Luty BA, McCammon JA (1991) Electrostatics and diffusion of molecules in solution: simulations with the University of Houston Brownian Dynamics program. Comp Phys Commun 62:187–197Google Scholar
  6. Ermak DL, McCammon JA (1978) Brownian dynamics with hydrodynamic interactions. J Chem Phys 69:1352–1360Google Scholar
  7. Garcia de la Torre J, Bloomfield VA (1981) Hydrodynamic properties of complex, rigid, biological macromolecules: theory and applications. Q Rev Biophys 14:81–139Google Scholar
  8. Head-Gordon T, Brooks CL (1987) The role of electrostatics in the binding of small ligands to enzymes. J Phys Chem 91:3342–3349Google Scholar
  9. Luty BA, Wade RC, Madura JD, Davis ME, Briggs JM, McCammon JA (1993) Brownian dynamics simulations of diffusional encounters between triose phosphate isomerase and glyceraldehyde phosphate: Electrostatic steering of glyceraldehyde phosphate. J Phys Chem 97:233–237Google Scholar
  10. Madura JD, Gilson, MEDMK, Wade RC, Luty BA, McCammon JA (1994) Biological applications of electrostatic calculations and brownian dynamics simulations. Rev Comput Chem 5:229–267Google Scholar
  11. McCammon JA, Harvey SC (1987) Dynamics of proteins and nucleic acids. Cambridge Univ. Press, CambridgeGoogle Scholar
  12. Northrup SH, Allison SA, McCammon JA (1984) Brownian dynamics simulation of diffusion-influence bimolecular reactions. J Chem Phys 80:1517–1524Google Scholar
  13. Northrup SH, Boles JO, Reynolds JCL (1987) Electrostatic effects in the brownian dynamics of association and orientation of heme proteins. J Phys Chem 91:5991–5998Google Scholar
  14. Oseen CW (1927) Neuere Methoden and Ergebnisse in der Hydrodynamik. Akademische Verlagsgesellschaft M B H, LeipzigGoogle Scholar
  15. Sharp KA (1994) Electrostatic interactions in macromolecules. Curr Opinion Struct Biol 4:234–239Google Scholar
  16. Sharp KA, Honig B (1990) Electrostatic interactions in macromolecules. Theory and applications. Annu Rev Biophys Chem 19:301–332Google Scholar
  17. Wade RC, Luty BA, Demchuk E, Madura JD, Davis ME, Briggs JM, McCammon JA (1994) Simulation of enzyme-substrate encounter with gated active sites. Nature Struct Biol 1:65–69Google Scholar
  18. Warwicker J, Watson HC (1982) Calculation of the electric potential in the active site cleft due to α-helix dipoles. J Mol Biol 157:671–679Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Jan Antosiewicz
    • 1
    • 2
  • James M. Briggs
    • 1
    • 2
  • J. Andrew McCammon
    • 1
    • 2
  1. 1.Department of Chemistry and BiochemistryUniversity of California at San DiegoLa JollaUSA
  2. 2.Department of PharmacologyUniversity of California at San DiegoLa JollaUSA
  3. 3.Department of BiophysicsUniversity of WarsawWarsawPoland

Personalised recommendations