Abstract
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.
Keywords
- 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.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Amadei, A., Linssen, A.B.M., Berendsen, H.J.C.: Essential Dynamics of Proteins. Proteins 17 (1993) 412–425
Baisera, M., Stepaniants, S., Izrailev, S., Oono, Y., Schulten, K.: Reconstructing Potential Energy Functions from Simulated Force-Induced Unbinding Processes. Biophys. J. 73 (1997) 1281–1287
Case, D.A.: Normal mode analysis of protein dynamics. Curr. Op. Struct. Biol. 4 (1994) 285–290
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) 79–88
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., Leiden
Gerstein, M., Lesk, A.M., Chothia, C: Structural Mechanisms for Domain Movements in Proteins. Biochemistry 33 (1994) 6739–6749
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) 3591–3600
Grubmüller, H.: Predicting Slow Structural Transitions in Macromolecular Systems-Conformational Flooding. Phys. Rev. E. 52 (1994) 2893–2906
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) 936–943
Head-Gordon, T., Brooks, C.L.: Virtual rigid body dynamics. Biopol. 31 (1991) 77–100
Helms, V., McCammon, J.A.: Kinase Conformations: A computational study of the effect of ligand binding. Prot. Sci. 6 (1997) 2336–2343
Jardetzky, O.: Protein dynamics and conformational transitions in allosteric proteins. Prog. Biophys. Mol. Biol. 65 (1996) 171–219
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) 57–95
McCammon, J.A., Gelin, B.R., Karplus, M., Wolynes, P.G.: The hinge-bending mode in lysozyme. Nature 262 (1976) 325–326
Moldyn Inc., 955 Massachusetts ave, 5th Floor, Cambridge, MA 02139-3180, USA
McCammon, J.A., Harvey, S.C.: Dynamics of Proteins and Nucleic Acids. Cambridge University Press, Cambridge (1987).
Oleander, R., Elber, R.: Calculation of classical trajectories with a very large time step: Formalism and numerical examples. J. Chem. Phys. 105 (1996) 9299–9315
Schlitter, J., Engels, M., Krüger, P.: Targeted molecular dynamics: A new approach for searching pathways of conformational transitions. J. Mol. Graph. 12 (1994) 84–89
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.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Helms, V., McCammon, J.A. (1999). Conformational Transitions of Proteins from Atomistic Simulations. In: Deuflhard, P., Hermans, J., Leimkuhler, B., Mark, A.E., Reich, S., Skeel, R.D. (eds) Computational Molecular Dynamics: Challenges, Methods, Ideas. Lecture Notes in Computational Science and Engineering, vol 4. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-58360-5_3
Download citation
DOI: https://doi.org/10.1007/978-3-642-58360-5_3
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-63242-9
Online ISBN: 978-3-642-58360-5
eBook Packages: Springer Book Archive