Proton Transfer through a Charged Conduit in Respiratory Complex I: Long-Range Effects and Conformational Gating
Luka Simsive, Oleksii Zdorevskyi, Vivek Sharma
Abstract
. By combining classical atomistic MD simulations with hybrid QM/MM free energy calculations, we identify several energetically favorable Grotthuss-competent proton transfer paths in the E channel region. As part of the long-range coupling in complex I, our calculations show that protonation of a single acidic amino acid residue in the distal MM surroundings can alter the dynamics of proton transfer in the E channel region. Additionally, we pinpoint the gating function of a highly conserved tyrosine residue in the E channel, which undergoes conformational flipping to establish an energetically favorable proton transfer path. In the context of the redox-coupled proton pumping mechanism of complex I, we propose a stepping-stone model of proton transfer through the E channel.