Proton Wire Dynamics in the Green Fluorescent Protein

Inside proteins, protons move on proton wires (PWs). Starting from the highest resolution X-ray structure available, we conduct a 306 ns molecular dynamics simulation of the (A-state) wild-type (wt) green fluorescent protein (GFP) to study how its PWs change with time. We find that the PW from the chromophore via Ser205 to Glu222, observed in all X-ray structures, undergoes rapid water molecule insertion between Ser205 and Glu222. Sometimes, an alternate Ser205-bypassing PW exists. Side chain rotations of Thr203 and Ser205 play an important role in shaping the PW network in the chromophore region. Thr203, with its bulkier side chain, exhibits slower transitions between its three rotameric states. Ser205 experiences more frequent rotations, slowing down when the Thr203 methyl group is close by. The combined states of both residues affect the PW probabilities. A random walk search for PWs from the chromophore reveals several exit points to the bulk, one being a direct water wire (WW) from the chromophore to...