Conformational Transitions of Proteins from Atomistic Simulations

Conference paper
Part of the Lecture Notes in Computational Science and Engineering book series (LNCSE, volume 4)


The function of many important proteins comes from their dynamic properties, and their ability to undergo conformational transitions. These may be small loop movements that allow access to the protein’s active site, or large movements such as those of motor proteins that are implicated with muscular extension. Yet, in spite of the increasing number of three-dimensional crystal structures of proteins in different conformations, not much is known about the driving forces of these transitions. As an initial step towards exploring the conformational and energetic landscape of protein kinases by computational methods, intramolecular energies and hydration free energies were calculated for different conformations of the catalytic domain of cAMP-dependent protein kinase (cAPK) with a continuum (Poisson) model for the electrostatics. In this paper, we will put the previous results into context and discuss possible extensions into the dynamic regime.


Molecular Dynamic Simulation Conformational Transition Atomistic Simulation Adenylate Kinase Binary Complex 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [Amadei et al. 1993]
    Amadei, A., Linssen, A.B.M., Berendsen, H.J.C.: Essential Dynamics of Proteins. Proteins 17 (1993) 412–425CrossRefGoogle Scholar
  2. [Baisera et al. 1997]
    Baisera, M., Stepaniants, S., Izrailev, S., Oono, Y., Schulten, K.: Reconstructing Potential Energy Functions from Simulated Force-Induced Unbinding Processes. Biophys. J. 73 (1997) 1281–1287CrossRefGoogle Scholar
  3. [Case 1996]
    Case, D.A.: Normal mode analysis of protein dynamics. Curr. Op. Struct. Biol. 4 (1994) 285–290CrossRefGoogle Scholar
  4. [Elamrani et al. 1996]
    Elamrani, S., Berry, M.B., Phillips Jr., G.N., McCammon, J.A.: Study of Global Motions in Proteins by Weighted Masses Molecular Dynamics: Adenylate Kinase as a Test Case. Proteins 25 (1996) 79–88CrossRefGoogle Scholar
  5. [Elcock et al. 1997]
    Elcock, A.H., Potter, M.J., McCammon, J.A.: Application of Poisson-Boltzmann Solvation Forces to Macromolecular Simulations. In “Computer Simulation of Biomolecular Systems,” Vol. 3, A.J. Wilkinson et al. eds., ESCOM Science Publishers B.V., LeidenGoogle Scholar
  6. [Gerstein et al. 1994]
    Gerstein, M., Lesk, A.M., Chothia, C: Structural Mechanisms for Domain Movements in Proteins. Biochemistry 33 (1994) 6739–6749CrossRefGoogle Scholar
  7. [Gilson et al. 1993]
    Gilson, M.K., Davis, M.E., Luty, B.A., McCammon, J.A.: Computation of Electrostatic Forces on Solvated Molecules Using the Poisson-Boltzmann Equation. J. Phys. Chem. 97 (1993) 3591–3600CrossRefGoogle Scholar
  8. [Grubmüller 1994]
    Grubmüller, H.: Predicting Slow Structural Transitions in Macromolecular Systems-Conformational Flooding. Phys. Rev. E. 52 (1994) 2893–2906CrossRefGoogle Scholar
  9. [Hayward et al. 1994]
    Hayward, S., Kitao, A., Gō, N.: Harmonic and anharmonic aspects in the dynamics of BPTI: A normal mode analysis and principal component analysis. Prot. Sci. 3 (1994) 936–943CrossRefGoogle Scholar
  10. [Head-Gordon and Brooks 1991]
    Head-Gordon, T., Brooks, C.L.: Virtual rigid body dynamics. Biopol. 31 (1991) 77–100CrossRefGoogle Scholar
  11. [Helms and McCammon 1997]
    Helms, V., McCammon, J.A.: Kinase Conformations: A computational study of the effect of ligand binding. Prot. Sci. 6 (1997) 2336–2343CrossRefGoogle Scholar
  12. [Jardetzky 1996]
    Jardetzky, O.: Protein dynamics and conformational transitions in allosteric proteins. Prog. Biophys. Mol. Biol. 65 (1996) 171–219CrossRefGoogle Scholar
  13. [Madura et al. 1995]
    Madura, J.D., Briggs, J.M., Wade, R.C., Davis, M.E., Luty, B.A., Hin, A., Antosiewicz, J., Gilson, M.K., Bagheri, B., Scott, L.R., McCammon, J.A.: Electrostatics and Diffusion of Molecules in Solution: Simulations with the University of Houston Brownian Dynamics Program. Comp. Phys. Comm. 91 (1995) 57–95CrossRefGoogle Scholar
  14. [McCammon et al. 1976]
    McCammon, J.A., Gelin, B.R., Karplus, M., Wolynes, P.G.: The hinge-bending mode in lysozyme. Nature 262 (1976) 325–326CrossRefGoogle Scholar
  15. [Moldyn 1997]
    Moldyn Inc., 955 Massachusetts ave, 5th Floor, Cambridge, MA 02139-3180, USAGoogle Scholar
  16. [McCammon and Harvey 1987]
    McCammon, J.A., Harvey, S.C.: Dynamics of Proteins and Nucleic Acids. Cambridge University Press, Cambridge (1987).CrossRefGoogle Scholar
  17. [Oleander and Elber 1996]
    Oleander, R., Elber, R.: Calculation of classical trajectories with a very large time step: Formalism and numerical examples. J. Chem. Phys. 105 (1996) 9299–9315CrossRefGoogle Scholar
  18. [Schlitter et al. 1994]
    Schlitter, J., Engels, M., Krüger, P.: Targeted molecular dynamics: A new approach for searching pathways of conformational transitions. J. Mol. Graph. 12 (1994) 84–89CrossRefGoogle Scholar
  19. [Vonrhein et al. 1995]
    Vonrhein, C., Schlauderer, G.J., Schulz, G.E.: Movie of the structural changes during a catalytic cycle of nucleoside monophosphate kinases. Structure 3 (1995) 483–490.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  1. 1.Department of Chemistry and BiochemistryUniversity of California at San DiegoLa JollaUSA

Personalised recommendations