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Copper binding sites in the C‐terminal domain of mouse prion protein: A hybrid (QM/MM) molecular dynamics study
Author(s) -
Colombo Maria Carola,
VandeVondele Joost,
Van Doorslaer Sabine,
Laio Alessandro,
Guidoni Leonardo,
Rothlisberger Ursula
Publication year - 2008
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21604
Subject(s) - copper , molecular dynamics , prion protein , chemistry , electron paramagnetic resonance , hyperfine structure , binding domain , crystallography , computational chemistry , binding site , physics , nuclear magnetic resonance , atomic physics , biochemistry , medicine , disease , organic chemistry , pathology
We present a hybrid QM/MM Car–Parrinello molecular dynamics study of the copper‐loaded C‐terminal domain of the mouse prion protein. By means of a statistical analysis of copper coordination in known protein structures, we localized the protein regions with the highest propensity for copper ion binding. The identified candidate structures were subsequently refined via QM/MM simulations. Their EPR characteristics were computed to make contact with the experimental data and to probe the sensitivity to structural and chemical changes. Overall best agreement with the experimental EPR data (Van Doorslaer et al., J Phys Chem B 2001; 105: 1631–1639) and the information currently available in the literature is observed for a binding site involving H187. Moreover, a reinterpretation of the experimental proton hyperfine couplings was possible in the light of the present computational findings. Proteins 2008. © 2007 Wiley‐Liss, Inc.