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Combining fragment homology modeling with molecular dynamics aims at prediction of Ca2+ binding sites in CaBPs

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Abstract

The family of calcium-binding proteins (CaBPs) consists of dozens of members and contributes to all aspects of the cell’s function, from homeostasis to learning and memory. However, the Ca2+-binding mechanism is still unclear for most of CaBPs. To identify the Ca2+-binding sites of CaBPs, this study presented a computational approach which combined the fragment homology modeling with molecular dynamics simulation. For validation, we performed a two-step strategy as follows: first, the approach is used to identify the Ca2+-binding sites of CaBPs, which have the EF-hand Ca2+-binding site and the detailed binding mechanism. To accomplish this, eighteen crystal structures of CaBPs with 49 Ca2+-binding sites are selected to be analyzed including calmodulin. The computational method identified 43 from 49 Ca2+-binding sites. Second, we performed the approach to large-conductance Ca2+-activated K+ (BK) channels which don’t have clear Ca2+-binding mechanism. The simulated results are consistent with the experimental data. The computational approach may shed some light on the identification of Ca2+-binding sites in CaBPs.

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Acknowledgments

The work is supported by National Natural Science Foundation of China Grants 11175055 to YZ, 11247010 to HA, and by Natural Science Foundation of Hebei Province grant C2012202079 to HA, A2011202129 to MJ.

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Authors and Affiliations

  1. Institute of Biophysics, Hebei University of Technology, Tianjin, China

    ChunLi Pang, TianGuang Cao, JunWei Li, MengWen Jia, SuHua Zhang, ShuXi Ren, HaiLong An & Yong Zhan

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  1. ChunLi Pang
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  2. TianGuang Cao
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Correspondence to Yong Zhan.

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Pang, C., Cao, T., Li, J. et al. Combining fragment homology modeling with molecular dynamics aims at prediction of Ca2+ binding sites in CaBPs. J Comput Aided Mol Des 27, 697–705 (2013). https://doi.org/10.1007/s10822-013-9668-0

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