TY - JOUR T1 - Unraveling the mechanism of proton translocation in the extracellular half-channel of bacteriorhodopsin JF - bioRxiv DO - 10.1101/031609 SP - 031609 AU - Xiaoxia Ge AU - M. R. Gunner Y1 - 2015/01/01 UR - http://biorxiv.org/content/early/2015/11/13/031609.abstract N2 - Bacteriorhodopsin, a light activated protein that creates a proton gradient in halobacteria, has long served as a simple model of proton pumps. Within bacteriorhodopsin, several key sites undergo protonation changes during the photocycle, moving protons from the higher pH cytoplasm to the lower pH extracellular side. The mechanism underlying the long-range proton translocation between the central (the retinal Schiff base SB216, D85 and D212) and exit clusters (E194 and E204) remains elusive. To obtain a dynamic view of the key factors controlling proton translocation, a systematic study using molecular dynamics simulation was performed for eight bacteriorhodopsin models varying in retinal isomer and protonation of the SB216, D85, D212 and E204. The orientation of the R82 side-chain is found to correlate with the protonation states of the residues in the EC. The side-chain reorientation of R82 modulates the hydrogen-bond network and consequently the pathway of proton transfer. Quantum mechanical intrinsic reaction coordinate calculations of proton-transfer in the methyl guanidinium-hydronium-hydroxide model system suggest that proton transfer through R82 requires an initial geometry permitting proton donation and acceptance by the same amine. In all the models, R82 can form proton wires with both the CC and the EC connected by the same amine. Alternatively, rare proton wires for proton transfer from the CC to the EC without involving R82 were found in an O’ state where the proton on D85 is transferred to D212. ER -