Mismatched ions indicate quantum effects in proteins

We present a large number of examples of sidechain interactions in which it appears at first that highly unfavorable positive charges are in close proximity. In particular, we examine pairs of arginines (resp., lysines) whose sidechain Cζ (resp., Nζ) atoms are very close. We screen PDB files to find such pairs for which there are no plausible counter ions. On the other hand, we show that invariably there are dehydrons in the vicinity of the likecharge pairs that can promote deprotonation of positively charged sidechains, eliminating the charge mismatch. The chemical functionality of dehydrons is articulated through the co-option of nearby water molecules which are turned into proton acceptors (chemical base). This provides a plausible explanation for the unusual motif. Close interactions between like-charged sidechains have been observed for many years [1, 2]. An example of nearby arginines is given in Figure 1 where the distance between the Cζ atoms (PDB code CZ) of the two arginines is only 3.26Å. Such interations have been explained by different effects. One possibility is that there is a counter ion nearby, and an additional explanation is solvation effects [1]. However, in the interaction depicted in Figure 1, the closest possible counter ion is nearly 10Å away (see Table 2 for more details.) Thus a third possibility is that one (or both) of the arginines becomes deprotonated and thus neutrally charged. This possibility was addressed in [3] where it was concluded that this is unlikely in certain cases where there are nearby counter ions. However, this leaves open the question of explaining such interactions in the absence of nearby counter ions. Here we propose an explanation of sidechain deprotonation that can account for such close encounters when there are no counter ions nearby. It is known that dehydrons functionalize water [4, 5, 6] by inducing chemical basicity which promotes deprotonation of sidechains. We