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Water Pathways in the Bacteriorhodopsin Proton Pump

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Abstract

Internal water molecules play key roles in the functioning of the light-driven bacteriorhodopsin proton pump. Of particular importance is whether during the proton-pumping cycle the critical water molecule w402 can relocate from the extracellular to the cytoplasmic side of the retinal Schiff base. Here, classical mechanical and combined quantum mechanical/molecular mechanical reaction path computations are performed to investigate pathways and energetic factors influencing w402 relocation. Hydrogen bonding between w402 and the negatively charged Asp85 and Asp212 largely opposes repositioning of the water molecule. In contrast, favorable contributions from hydrogen bonding of w402 with the Schiff base and Thr89 and from the untwisting of the retinal polyene chain lower the energetic cost for water relocation. The delicate balance between the competing contributions underlies the need for highly accurate calculations and structural information.

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Acknowledgments

This work was financed in part by the Deutsche Forschungsgemeinschaft (SM 63/7). ANB was supported by grants GM74637 and GM-86685 from the National Institutes of General Medical Sciences. JCS was supported by a Laboratory-Directed Research and Development grant in Systems Biology to Oak Ridge National Laboratory from the U.S. Department of Energy.

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  1. Ana-Nicoleta Bondar

    Present address: Department of Physics, Freie Universität Berlin, Arnimallee 14, 14195, Berlin, Germany

Authors and Affiliations

  1. Department of Physiology and Biophysics, Medical Science I, University of California at Irvine, Irvine, CA, 92697-4560, USA

    Ana-Nicoleta Bondar

  2. Computational Molecular Biophysics, IWR, University of Heidelberg, 69120, Heidelberg, Germany

    Ana-Nicoleta Bondar & Jeremy C. Smith

  3. Molecular Biophysics Department, German Cancer Research Center, Im Neuenheimer Feld 580, 69120, Heidelberg, Germany

    Ana-Nicoleta Bondar

  4. Computational Biochemistry IWR, University of Heidelberg, 69120, Heidelberg, Germany

    Stefan Fischer

  5. University of Tennessee/Oak Ridge National Laboratory Center for Molecular Biophysics, PO Box 2008 MS6164, Oak Ridge, TN, 37831-6164, USA

    Jeremy C. Smith

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  1. Ana-Nicoleta Bondar
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Correspondence to Ana-Nicoleta Bondar or Jeremy C. Smith.

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Bondar, AN., Fischer, S. & Smith, J.C. Water Pathways in the Bacteriorhodopsin Proton Pump. J Membrane Biol 239, 73–84 (2011). https://doi.org/10.1007/s00232-010-9329-3

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