Send to

Choose Destination
J Chem Phys. 2016 Mar 14;144(10):105102. doi: 10.1063/1.4943130.

Comparing allosteric transitions in the domains of calmodulin through coarse-grained simulations.

Author information

Department of Physics, Kent State University, Kent, Ohio 44242, USA.


Calmodulin (CaM) is a ubiquitous Ca(2+)-binding protein consisting of two structurally similar domains with distinct stabilities, binding affinities, and flexibilities. We present coarse grained simulations that suggest that the mechanism for the domain's allosteric transitions between the open and closed conformations depends on subtle differences in the folded state topology of the two domains. Throughout a wide temperature range, the simulated transition mechanism of the N-terminal domain (nCaM) follows a two-state transition mechanism while domain opening in the C-terminal domain (cCaM) involves unfolding and refolding of the tertiary structure. The appearance of the unfolded intermediate occurs at a higher temperature in nCaM than it does in cCaM consistent with nCaM's higher thermal stability. Under approximate physiological conditions, the simulated unfolded state population of cCaM accounts for 10% of the population with nearly all of the sampled transitions (approximately 95%) unfolding and refolding during the conformational change. Transient unfolding significantly slows the domain opening and closing rates of cCaM, which can potentially influence its Ca(2+)-binding mechanism.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Institute of Physics
Loading ...
Support Center