Simulation of catalytic water activation in mitochondrial F1-ATPase using a hybrid quantum mechanics/molecular mechanics approach: an alternative role for β-Glu 188

Biochemistry. 2013 Feb 5;52(5):959-66. doi: 10.1021/bi301109x. Epub 2013 Jan 25.


The use of quantum mechanics/molecular mechanics simulations to study the free energy landscape of the water activation at the catalytic site of mitochondrial F(1)-ATPase affords us insight into the generation of the nucleophile OH(-) prior to ATP hydrolysis. As a result, the ATP molecule was found to be the final proton acceptor. In the simulated pathway, the transfer of a proton to the nucleotide was not direct but occurred via a second water molecule in a manner similar to the Grotthuss mechanism proposed for proton diffusion. Residue β-Glu 188, previously described as the putative catalytic base, was found to be involved in the stabilization of a transient hydronium ion during water activation. Simulations in the absence of the carboxylate moiety of β-Glu 188 support this role.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Cattle
  • Glutamic Acid / chemistry
  • Glutamic Acid / metabolism*
  • Hydrolysis
  • Mitochondria / chemistry
  • Mitochondria / enzymology*
  • Molecular Dynamics Simulation*
  • Proton-Translocating ATPases / chemistry
  • Proton-Translocating ATPases / metabolism*
  • Protons
  • Quantum Theory
  • Water / chemistry
  • Water / metabolism*


  • Protons
  • Water
  • Glutamic Acid
  • Adenosine Triphosphate
  • Proton-Translocating ATPases