This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shepherd, C. M. Articles by Vogel, H. J. Search for Related Content PubMed PubMed Citation Articles by Shepherd, C. M. Articles by Vogel, H. J.

A Molecular Dynamics Study of Ca²⁺-Calmodulin: Evidence of Interdomain Coupling and Structural Collapse on the Nanosecond Timescale

Structural Biology Research Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada

Correspondence: Address reprint requests to Hans J. Vogel, Tel.: 403-220-6006; Fax: 403-289-9311; E-mail: vogel{at}ucalgary.ca.

A 20-ns molecular dynamics simulation of Ca²⁺-calmodulin (CaM) in explicit solvent is described. Within 5 ns, the extended crystal structure adopts a compact shape similar in dimension to complexes of CaM and target peptides but with a substantially different orientation between the N- and C-terminal domains. Significant interactions are observed between the terminal domains in this compact state, which are mediated through the same regions of CaM that bind to target peptides derived from protein kinases and most other target proteins. The process of compaction is driven by the loss of helical structure in two separate regions between residues 75–79 and 82–86, the latter being driven by unfavorable electrostatic interactions between acidic residues. In the first 5 ns of the simulation, a substantial number of contacts are observed between the first helix of the N-terminal domain and residues 74–77 of the central linker. These contacts are correlated with the closing of the second EF-hand, indicating a mechanism by which they can lower calcium affinity in the N-terminal domain.

This article has been cited by other articles:

				A. Ganoth, R. Friedman, E. Nachliel, and M. Gutman A Molecular Dynamics Study and Free Energy Analysis of Complexes between the Mlc1p Protein and Two IQ Motif Peptides Biophys. J., October 1, 2006; 91(7): 2436 - 2450. [Abstract] [Full Text] [PDF]

				E. Project, R. Friedman, E. Nachliel, and M. Gutman A Molecular Dynamics Study of the Effect of Ca2+ Removal on Calmodulin Structure Biophys. J., June 1, 2006; 90(11): 3842 - 3850. [Abstract] [Full Text] [PDF]

				C. Kobayashi and S. Takada Protein Grabs a Ligand by Extending Anchor Residues: Molecular Simulation for Ca2+ Binding to Calmodulin Loop Biophys. J., May 1, 2006; 90(9): 3043 - 3051. [Abstract] [Full Text] [PDF]