Schematic representations of the Grotthuss and Grotthuss-like mechanism for proton channeling.

<p>The amino acid labels indicated on the right side serve as positional references. The Mg²⁺ (green sphere) is coordinated with three water molecules and three Oε1 side chain oxygen atoms based on the symmetry-related Gln 3014 (green circles). <b>A.</b> When the external capsid pH is basic with to respect the internal region, protons jump between adjacent waters as indicated by the arrows. Under this condition, H⁺ holes can migrate from the capsid exterior (overcoming a low energetic barrier), showing a concerted Grotthuss-like mechanism of proton jumps. This sequence corresponds to panels A-G of <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006082#pcbi.1006082.g003" target="_blank">Fig 3</a>. <b>B.</b> When the outer solvent region is acidic with respect to the capsid interior (higher hydronium concentration), proton migration occurs between hydronium and H₂O molecules. A proton that binds to a hydronium in the upper bulk solvent can go down two steps along the external portion of the water wire (ΔE ~ -4.2 kcal/mol). When this proton migration occurs, it stops at the water close to the water molecule coordinated to the Mg²⁺. From this point down, the water wire is disrupted due to the increase in distance between the hydronium and the inner-most proximal water molecule (~0.36 nm), which is precisely the one linked to the metal cation. Breaking of the water wire constitutes the electrical impediment for the proton to proceed downward and reach the capsid internal solvent. Positive and negative numbers indicate the approximate energy value (in kcal) that corresponds to each proton jump. For clarity, only a subset of the 536 atoms involved in the calculation was included in these panels.