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Targeted molecular dynamics (TMD) of the full-length KcsA potassium channel: on the role of the cytoplasmic domain in the opening process

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Abstract

Some recent papers clearly indicate that the cytoplasmic domain of KcsA plays a role in pH sensing. We have performed, for the first time, a targeted molecular dynamics (TMD) simulation of the opening of full-length KcsA at pH 4 and pH 7, with a special interest for the cytoplasmic domain. Association energy calculations show a stabilization at pH 7 confirming that the protonation of some amino-acids at pH 4 in this domain plays a role in the opening process. A careful analysis of the pH dependent charges borne by residues in the cytoplasmic domain and their interactions confirms some literature experimental data and permits to give further insight into the role played by some of them in the opening process.

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Notes

  1. Except for the full systems simulations where residues 113 and 114 were not restrained since they are located at the border between TM and cytoplasmic domains.

  2. The global bending of the cytoplasmic domain was defined by the angle between the mass-weighted backbone atoms of residues Val48, Ala111 and Asp120 of the four units.

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Acknowledgments

The China Scholarship Council is gratefully acknowledged for granting a PhD scholarship to Yan LI.

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Authors and Affiliations

  1. Department of Chemistry, Lanzhou University, Lanzhou, Gansu, 730000, People’s Republic of China

    Yan Li & Ruisheng Zhang

  2. School of Information Science and Engineering, Lanzhou University, Lanzhou, Gansu, 730000, People’s Republic of China

    Ruisheng Zhang & Rong**g Hu

  3. Univ Paris Diderot, Sorbonne Paris Cité, ITODYS, UMR CNRS 7086, 15 rue J-A. de Baïf, 75013, Paris, France

    Yan Li, Florent Barbault & Michel Delamar

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  1. Yan Li
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Correspondence to Michel Delamar.

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Li, Y., Barbault, F., Delamar, M. et al. Targeted molecular dynamics (TMD) of the full-length KcsA potassium channel: on the role of the cytoplasmic domain in the opening process. J Mol Model 19, 1651–1666 (2013). https://doi.org/10.1007/s00894-012-1726-3

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