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Docking of calcium ions in proteins with flexible side chains and deformable backbones

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Abstract

A method of docking Ca2+ ions in proteins with flexible side chains and deformable backbones is proposed. The energy was calculated with the AMBER force field, implicit solvent, and solvent exposure-dependent and distance-dependent dielectric function. Starting structures were generated with Ca2+ coordinates and side-chain torsions sampled in 1000 Å3 cubes centered at the experimental Ca2+ positions. The energy was Monte Carlo-minimized. The method was tested on fourteen Ca2+-binding sites. For twelve Ca2+-binding sites the root mean square (RMS) deviation of the apparent global minimum from the experimental structure was below 1.3 and 1.7 Å for Ca2+ ions and side-chain heavy atoms, respectively. Energies of multiple local minima correlate with the RMS deviations from the X-ray structures. Two Ca2+-binding sites at the surface of proteinase K were not predicted, because of underestimation of Ca2+ hydration energy by the implicit-solvent method.

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Abbreviations

MCM:

Monte Carlo-minimization

RMSD:

Root mean square deviation

AGM:

Apparent global minimum

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Acknowledgments

We thank Denis B. Tikhonov for helpful discussions. The study was supported by the Canadian Institutes of Health Research (grant MOP-53229 to BSZ). This work was made possible by the facilities of the Shared Hierarchical Academic Research Computing Network (SHARCNET: http://www.sharcnet.ca).

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  1. Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada

    Ricky C. K. Cheng & Boris S. Zhorov

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  1. Ricky C. K. Cheng
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Correspondence to Boris S. Zhorov.

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Cheng, R.C.K., Zhorov, B.S. Docking of calcium ions in proteins with flexible side chains and deformable backbones. Eur Biophys J 39, 825–838 (2010). https://doi.org/10.1007/s00249-009-0561-7

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  • DOI: https://doi.org/10.1007/s00249-009-0561-7

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