Quantum molecular dynamics simulation of proton transfer in cytochrome c oxidase

Proton transfer/translocation is studied in cytochrome c oxidase (CcO) by a combination of quantum mechanics (QM) for the transferring protons and classical molecular dynamics (MD) for the protein and solvent. The possibility of a glutamate, Glu286 in the Rhodobacter sphaeroides numbering scheme, acting as a rely point for proton translocation is investigated. The MD finds a hydrogen-bonded cycle of two waters and the carboxylate oxygens of Glu286. The possibility of protonating Glu286 to form neutral GluH is studied and we find that, as experimentally inferred, this glutamate can spend most of its time as GluH. Since translocation relies on the presence of water chains within CcO channels, MD is used to assess their formation. Glu286 and Mg(2+) can be connected by continuous hydrogen-bonded chains that are robust, though transient, and the protein appears spongy above (toward the outer membrane) the Mg(2+). In contrast, the D-channel spanning Asp132, close to the inner membrane surface, to Glu286, forms water chains that are much sparser and do not continuously connect these residues. Rather, there are chains spanning Glu286 to the vicinity of Asn140, and other more robust and ramified water structures that connect Asp132 with waters close to Asn140.