Atomic charges of Cl- ions confined in a model Escherichia coli ClC-Cl-/H+ ion exchanger: a density functional theory study

We present extensive semi-empirical and pseudo-potential density functional theory calculations dedicated to analyse the stability, charge density distribution and migration behaviour of Cl- ions confined in model Escherichia coli (ec) ClC-Cl-/H+ ion-exchangers. Following recent high-resolution crystal structure determination in these kinds of systems, we use a finite-cluster model approach and construct various chemically simplified pore structures made of a glutamate residue -CH2-CH2-COO- (E148) and its closets 15, 19, 23 and 26 amino acids into which the Cl- ions will be confined. We reveal the sequence of molecular rearrangements induced on the E148 chain, which blocks the middle of the conduction pathway, leading to the pore opening. The -CH2-CH2-COO- fragment shows notable variations in its average charge density for small changes in the intra-cellular environment varying from -0.4e to -0.3e to -0.1e in the presence of zero, one and two confined Cl- ions, respectively, a result that reveals an interesting functionality of the E148 chain during Cl- conduction. We also obtain complex fluctuations in the ionic charge of the confined Cl- ions varying from approximate to-0.7e to -0.2e, which deviate significantly from the value (-1e) usually used in classical simulations. By attaching a single H species to one of the oxygens of the glutamate group, we obtain that the -CH2-CH2-COOH fragment has now a small effective charge of approximate to+0.25e. The energy barriers opposing the exit of the Cl- ions from our considered ion-exchangers vary from 0.65 eV to 4.7 eV, the smallest values being obtained for model structures exhibiting a high degree of flexibility and having protonated E148 fragments. Our results reinforce previous findings and provide additional physical insight, at the atomic level, on the gating process. Finally, we underline the importance of using electronically polarisable force fields to describe the transport of anionic species through this kind of molecular constrictions.