This Article Full Text Full Text (PDF) Supplement All Versions of this Article: biophysj.107.109512v1 93/11/3762    most recent 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 Pushie, M. J. Articles by Vogel, H. J. Search for Related Content PubMed PubMed Citation Articles by Pushie, M. J. Articles by Vogel, H. J.

Molecular Dynamics Simulations of Two Tandem Octarepeats from the Mammalian Prion Protein: Fully Cu²⁺-bound and Metal-Free Forms

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

Correspondence: Address reprint requests to Hans J. Vogel, Dept. of Biological Sciences, University of Calgary, 2500 University Dr. NW, Calgary, Alberta, T2N 1N4, Canada. Tel.: 403-220-6006; Fax: 403-289-9311; E-mail: vogel{at}ucalgary.ca.

Molecular dynamics simulations have been conducted on a model fragment (Ac-PHGGGWGQPHGGGW-NH₂) of the prion protein octarepeat domain, both in the Cu²⁺-bound and metal-free forms. The copper-bound models are based on the consensus structure of the core Cu²⁺-binding site of an individual octarepeat, relevant to the fully Cu²⁺-occupied prion protein octarepeat region. The model peptides contain Cu²⁺ bound through a His imidazole ring and two deprotonated amide N-atoms in the peptide backbone supplied by the following two Gly residues. Both the copper-bound and metal-free models have been simulated with the OPLS all-atom force field with the GROMACS molecular dynamics package. These simulations, with two tandem copper-binding sites, represent the minimum model necessary to observe potential structuring between the copper-binding sites in the octarepeat region. The GWGQ residues constitute a flexible linker region that predominantly adopts a turn, serving to bring adjacent His residues into close proximity. The consequent formation of stable structures demonstrates that the copper-bound octarepeat region allows the copper-coordinating sites to come into van der Waals contact, packing into particular orientations to further stabilize the bend in the GWGQ linker region.

This article has been cited by other articles:

				M. J. Pushie and H. J. Vogel Modeling by Assembly and Molecular Dynamics Simulations of the Low Cu2+ Occupancy Form of the Mammalian Prion Protein Octarepeat Region: Gaining Insight into Cu2+-Mediated {beta}-Cleavage Biophys. J., December 1, 2008; 95(11): 5084 - 5091. [Abstract] [Full Text] [PDF]