Allosteric Conformational Transition in Adenylate Kinase: Dynamic Correlations and Implication for Allostery

Ming S. Liu; Billy D. Todd; Richard J. Sadus

doi:10.1071/CH09449

RESEARCH FRONT

Previous Next Contents Vol 63(3)

Allosteric Conformational Transition in Adenylate Kinase: Dynamic Correlations and Implication for Allostery

Ming S. Liu ^A ^B ^C , Billy D. Todd ^B and Richard J. Sadus ^B

+ Author Affiliations

- Author Affiliations

^A CSIRO, Mathematics, Informatics and Statistics, Private Bag 33, Clayton South, Vic. 3169, Australia.

^B Centre for Molecular Simulation, Swinburne University of Technology, P.O. Box 218, Hawthorn, Vic. 3122, Australia.

^C Corresponding author. Email: ming.liu@csiro.au

Australian Journal of Chemistry 63(3) 405-412 https://doi.org/10.1071/CH09449
Submitted: 27 August 2009 Accepted: 10 February 2010 Published: 26 March 2010

Abstract

An essential aspect of protein science is to determine the deductive relationship between structure, dynamics, and various sets of functions. The role of dynamics is currently challenging our understanding of protein functions, both experimentally and theoretically. To verify the internal fluctuations and dynamics correlations in an enzyme protein undergoing conformational transitions, we have applied a coarse-grained dynamics algorithm using the elastic network model for adenylate kinase. Normal mode analysis reveals possible dynamical and allosteric pathways for the transition between the open and the closed states of adenylate kinase. As the ligands binding induces significant flexibility changes of the nucleotides monophosphate (NMP) domain and adenosine triphosphate (ATP) domain, the diagonalized correlation between different structural transition states shows that most correlated motions occur between the NMP domain and the helices surrounding the ATP domain. The simultaneous existence of positive and negative correlations indicates that the conformational changes of adenylate kinase take place in an allosteric manner. Analyses of the cumulated normal mode overlap coefficients and long-range correlated motion provide new insights of operating mechanisms and dynamics of adenylate kinase. They also suggest a quantitative dynamics criterion for determining the allosteric cooperativity, which may be applicable to other proteins.

Acknowledgements

This work is partly supported by the Australian Research Council (ARC Discovery Project: DP0557991). Generous allocations of computing resources from the Australian and Victorian Partnerships for Advanced Computing are also acknowledged.

References

Allosteric Conformational Transition in Adenylate Kinase: Dynamic Correlations and Implication for Allostery

Abstract

Acknowledgements

Subscriber Login