Kinetics of hydrogen migration and string of conformation transformation for pyruvic acid under bioelectric stimulation
Authors: Feng Rui-zhi , Li Xiao-jiang , Liu Ai-chuan , Kuo Jian 
Published: February 2025

Abstract

Context
The competition between the proton migration and conformational transformation of the biomolecules stimulated by bioelectric currents is of importance for maintaining the normal biochemical reaction process of organisms. To reveal the biochemical reaction mechanism of pyruvic acid under the bioelectric currents, the effect of external electric field on the bi-proton cooperativity migration of the dimer was investigated, accompanied by a comparison with the finite temperature string (FTS) with enhanced sampling for the molecular conformational transformation. The results indicate that the influences of the external electric fields along the x- and y-axis directions on the transition state are more significant than those on the z-axis direction, and that of the x-axis direction on the bi-proton cooperativity migration is the most significant. The reaction induced by the external electric fields along the + x- or + y- direction tends to form the products from the bi-proton cooperativity migration in which the hydroxyl group is on the same side as the ‒CH3 or ‒CF3 group. There are some good linear relationships between the bond length changes, atoms in molecules (AIM) changes, surface electrostatic potential statistical changes of the transition state, potential barrier and free energy changes and the external electric field strengths. The spatial order parameters (φ, ψ) of the conformational transformation of pyruvic acid can be quickly converged through the umbrella sampling and parameter averaging, thereby obtaining the potential energy surface of potential of mean force (PMF) for the conformational transformation. Under the bioelectricity, the activation energies for the double proton migration of pyruvic acid molecules are much greater than the PMF barriers for its conformational transformation, indicating that under the stimulation of bioelectricity, the majority of pyruvic acid molecules undergo the conformational transformation rather than through the mechanism of the double proton cooperativity migration. The direction of bioelectricity greatly affects the cooperativity migration, while it has little effect on the order parameters and PMF of the conformational transformation of pyruvic acid molecules. This study has important theoretical significance and scientific value for the further investigations on proton migration and conformational transformation in the biochemical reaction processes for the sports human science.
Methods
The effects of external electric fields on the bi-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 FTS model with enhanced sampling for molecular conformational transformation was constructed, and the PMF of pyruvate conformational transformation under external electric field was studied by using the CHARMM22 force field from NAMD software packages, and PLUMED program.