Proton conduction by a chain of water molecules in carbonic anhydrase

Ah initio and density functional theory (DFT) calculations are used to investigate a (NH3)(3)Zn2+. . . (OH2)(n). . NH3 system that models the proton conduction, via a chain of water molecules, from a Zn2+ ion to a His residue some distance removed. The optimal configuration of this chain, with n = 3, contains a number of fairly short H-bonds separating the water molecules. The conduction of a proton from the Zn-bound water to the terminal N-acceptor is energetically favored by a concerted process wherein all protons are in flight from one molecule to the next along the chain, at approximately the same time. This optimal process also includes the shortening of each H-bond as the donor and acceptor move toward one another at the midpoint of the transfer as well as small alterations in the distance between Zn and its various ligands. The barrier for the conduction process is not adversely affected by a lengthening of the chain to include as many as five waters. However, the process is slowed considerably if additional H-bonds are formed between members of the chain and peripheral molecules. The reorientation of the chain that places the ultimate N-acceptor at an angle of greater than some 30 degrees from the Zn- -O axis of the Zn-bound water can also slow the conduction process.