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This article is part of the supplement: BioSysBio 2007: Systems Biology, Bioinformatics, Synthetic Biology

Open Access Poster presentation

Molecules for memory: modelling CaMKII

Melanie Stefan* and Nicolas Le Novere

Author Affiliations

EMBL – European Bioinformatics Institute (EBI), Hinxton, Cambridge, CB10 1SD, UK

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BMC Systems Biology 2007, 1(Suppl 1):P40  doi:10.1186/1752-0509-1-S1-P40

The electronic version of this article is the complete one and can be found online at:

Published:8 May 2007

© 2007 Stefan and Le Novere; licensee BioMed Central Ltd..


Long-term modifications of synaptic strength, such as long-term potentiation (LTP) or long-term depression (LTD) are thought to underlie some forms of learning and memory. At the excitatory glutamate synapse, LTP is dependent on calcium influx through the N-methyl-D-aspartate (NMDA) receptor and subsequent activation of calcium/calmodulin-dependent protein kinase II (CaMKII). The NMDA receptor, CaMKII, and its activator calmodulin are all embedded in a complex hyperstructure consisting of more than 180 molecules [1] that acts as as a "synaptic plasticity nanomachine". Our current work aims at exploring CaMKII function in the context of the NMDA receptor complex

Materials and methods

We used StochSim [2] to carry out stochastic single-particle simulations. Molecules react with each other according to probabilities computed from kinetic constants. An important feature of StochSim is that different states (e.g. open/closed, phosphorylated/unphosphorylated at a specific site) or combinations of different states can be represented. Reactions can modify the state of a molecule, and likewise, the state of a molecule can have an influence on its propensity to participate in a given reaction.


A series of models of CaMKII has been created to explore the interplay between phosphorylation, interaction with other proteins, conformational change and kinase activity. Simulations have been carried out using the stochastic simulator StochSim [2]. So far, the model was successful in explaining the effect of calmodulin binding and Thr286 autophosphorylation on CaMKII conformation. Furthermore, it suggests functional implications for CaMKII binding to the NR2B subunit of the NMDA receptor.


A series of models have been created to explore CaMKII function in the context of the NMDA receptor complex. First simulations using StochSim confirm mechanisms described in the experimental literature and suggest further predictions about the system. Future work includes the extension of the model to include a larger number of processes and interaction partners.


  1. Collins MO, Yu L, Coba MP, Husi H, Campuzano I, Blackstock W, Choudhary JS, Grant SGN: Molecular characterization and comparison of the components and multiprotein complexes in the postsynaptic proteome.

    J Neurochem 2006, 97:16-23. PubMed Abstract | Publisher Full Text OpenURL

  2. Morton-Firth CJ: Stochastic Simulation of Cell Signalling Pathways. PhD thesis. University of Cambridge; 1998. OpenURL