Modeling protonated water networks in bacteriorhodopsin

A model is constructed to investigate in atomistic detail the structure and dynamics of protonated water networks on the extracellular side of the transmembrane proton pump bacteriorhodopsin. The protein is embedded in a solvated lipid bilayer membrane described by established force fields. Most importantly, the protonated water network is treated in the framework of a mixed density functional electronic structure theory/molecular mechanics approach. This QM/MM Car–Parrinello molecular dynamics approach employed allows for stable dynamics on a picosecond time scale. The structural building process, force field parameterizations and subsequent equilibration of the total system consisting of the protein, the lipid membrane and the hydration layer is described in detail followed by a QM/MM simulation of the protonated water network. It is found that hydrogen-bonded networks around both H3O+ and H5O2+ cores can be stabilized in the protein matrix, leading to so-called Eigen and solvated Zundel complexes, H3O+· (H2O)3 and H5O2+·(H2O)4, respectively. It turns out that both complexes behave qualitatively similarly to the gas phase, implying that the H5O2+ core displays an essentially symmetric hydrogen bond with the excess proton being equally shared between two water molecules. The dynamics of this hydrogen bond is found to be complex featuring slow large-amplitude motion of the central proton as well as complex dynamics of the protonated water cluster hydrogen bonds formed with the protein matrix. These findings are consistent with the proposal that an essential component of the so-called proton release group “XH” could consist of a protonated water network stabilized by polar aminoacids.