Hydroxide Ion Mechanism for Long-Range Proton Pumping in the Third Proton Transfer of Bacteriorhodopsin

Junichi Ono, Chika Okada, Hiromi Nakai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


In bacteriorhodopsin, representative light-driven proton pump, five proton transfers yield vectorial active proton translocation, resulting in a proton gradient in microbes. Third proton transfer occurs from Asp96 to the Schiff base on the photocycle, which is expected to be a long-range proton transfer via the Grotthuss mechanism through internal water molecules. Here, large-scale quantum molecular dynamics simulations are performed for the third proton transfer, where all the atoms (∼50000 atoms) are treated quantum-mechanically. The simulations demonstrate that two reaction paths exist along the water wire, namely, via hydronium and via hydroxide ions. The free energy analysis confirms that the path via hydroxide ions is considerably favorable and consistent with the observed lifetime of the transient water wire. Therefore, the proposed hydroxide ion mechanism, as in the first proton transfer, is responsible for the third long-range proton transfer.

Original languageEnglish
Article numbere202200109
Issue number22
Publication statusPublished - 2022 Nov 18


  • molecular dynamics
  • proteins
  • proton transport
  • quantum chemistry
  • reaction mechanisms

ASJC Scopus subject areas

  • Atomic and Molecular Physics, and Optics
  • Physical and Theoretical Chemistry


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