Electrostatic and proton–electron interaction in membrane-bound charge transfer proteins under external electric fields: a computational study

Membrane-bound charge transfer proteins play essential roles in energy conversion and biological redox processes, yet their response to external electric fields remains unexplored. We have investigated the NrfH subunit of the nitrite reductase complex from <i>Desulfovibrio vulgaris</i> under static electric fields, motivated by its potential integration into bio-nanoelectronic devices. Using a multiscale computational framework, classical molecular dynamics with constant pH sampling, continuum dielectric theory, and Laplace/Poisson solvers structural stability, voltage distribution, p<i>K</i>_a modulation, and electron-proton coupling have been investigated. The obtained results show that NrfH maintains structural integrity up to ±100 mV nm^-1, with voltage drop localized mainly within the membrane or protein interior. External fields shift the p<i>K</i>_a of titratable residues by up to one unit, but only Asp76, Lys65, and Lys104 undergo protonation state changes. Electron-proton coupling energies are generally smaller than <i>k</i>_B<i>T</i>, indicating weak energetic linkage between heme redox states and protonation. These findings clarify the electrostatic resilience of NrfH and suggest its application as an electron-conducting element in nanoscale bioelectronic platforms.