Context <p>To reveal the biochemical mechanism of pyruvic acid under the bioelectric currents, the effect of the external electric field on the intermolecular double-proton cooperativity migration was investigated for the dimer, accompanied by a comparison of the conformation transformation. The results indicate that the influences of the external electric fields on the transition state of the proton migration, i.e., the changes in the molecular structures, atoms in molecules, surface electrostatic potentials, and potential barriers, are closely related to the directions of the fields. The spatial order parameters of the conformation transformation of pyruvic acid can be quickly converged through the umbrella sampling and parameter averaging, thereby obtaining the potential energy surface of the potential of mean force. Under the strong external electric field, the barrier heights of the double-proton cooperativity migration are close to the free energy change of the conformation transformation, indicating the competition between the proton cooperativity transfer and conformation transformation. This study is of importance for revealing furthermore the essence of the competition between the proton migration and conformation transformation of the biomolecules stimulated by the bioelectric currents.</p> Methods <p>The effects of external electric fields on the double-proton cooperativity migration reaction pathway, potential barrier, and rate constant of the pyruvic acid dimer were studied using the M06-2X/6-311++G**, M06-2X/aug-cc-pVTZ, and CCSD(T)/6-311++G(2d,p) methods by using Gaussian 09 packages. A chaotic finite temperature string model with enhanced sampling for molecular conformation transformation was constructed, and the free energy change of conformation transformation under external electric field was studied by the finite temperature string (FTS) method with the CHARMM22 force field from NAMD software packages and PLUMED program.</p>