Hydrated Excess Protons Can Create Their Own Water Wires

Abstract

Grotthuss shuttling of an excess proton charge defect through hydrogen bonded water networks has long been the focus of theoretical and experimental studies. In this work we show that there is a related process in which water molecules move (“shuttle”) through a hydrated excess proton charge defect in order to wet the path ahead for subsequent proton charge migration. This process is illustrated through reactive molecular dynamics simulations of proton transport through a hydrophobic nanotube, which penetrates through a hydrophobic region. Surprisingly, before the proton enters the nanotube, it starts “shooting” water molecules into the otherwise dry space via Grotthuss shuttling, effectively creating its own water wire where none existed before. As the proton enters the nanotube (by 2–3 Å), it completes the solvation process, transitioning the nanotube to the fully wet state. By contrast, other monatomic cations (e.g., K+) have just the opposite effect, by blocking the wetting process and making the nanotube even drier. As the dry nanotube gradually becomes wet when the proton charge defect enters it, the free energy barrier of proton permeation through the tube via Grotthuss shuttling drops significantly. This finding suggests that an important wetting mechanism may influence proton translocation in biological systems, i.e., one in which protons “create” their own water structures (water “wires”) in hydrophobic spaces (e.g., protein pores) before migrating through them. An existing water wire, e.g., one seen in an X-ray crystal structure or MD simulations without an explicit excess proton, is therefore not a requirement for protons to transport through hydrophobic spaces.

Protonation-State-Dependent Communication in Cytochrome c Oxidase

“…Moreover, it has been observed that the presence of an excess proton in channel-like environments (such as carbon nanotubes) has a wetting effect, i.e., results in an increased number of water molecules inside the channel and therefore in a significant change of the water network (38). In previous MD simulations (11) and in those presented in this work, such an effect is indeed observed.…”

Origin of proton affinity to membrane/water interfaces

“…Another explanation may be that hydrated excess protons create their own water wires parallel to the membrane boundary. Such an effect has been observed in silico for proton transport through a hydrophobic nanotube 36 . It could explain why Δ G ‡ r is so much larger than the previously calculated free energy difference Δ G for passing from close proximity of the phosphate moieties to the bulk.…”

QM/MM free energy simulations: recent progress and challenges

“…134 It was found that the presence of the excess proton at one end of the nanotube induces spontaneous wetting of the tube and facilitates the subsequent proton transfer; interestingly, such favorable wetting behavior was not observed with other monovalent cations (e.g., Na + ) or a classical model of the hydronium ion (H 3 O + ), suggesting that the delocalized nature of the excess proton in water is essential. This delocalized nature is captured in our study with the use of a QM model (DFTB3), and the relatively similar barrier heights between 3OB and 3OBw suggests that the qualitative behavior is not highly sensitive to the quantitative description of proton solvation.…”

“…134 ) has important implications to proton transfer in biomolecules. Proton transfer pathways are often identified by examining hydrogen bonding networks 135,136 visible in protein structures from crystallography or equilibrium MD simulations in the absence of an excess proton.…”