Transmembrane Anion Transport Mediated by Halogen Bonds: Using Off-Center Charges

Synthetic anion transporters are promising therapeutic agents designed to emulate the specialized role of certain transmembrane proteins that maintain the ion concentration in cells. In the last few years, besides hydrogen bonds and ion pairs, halogen bonds have also been explored to promote the association between the synthetic molecule and the anion and their subsequent transport. This interaction is due to an anisotropic charge distribution on the halogen, and therefore, modeling halogen bonds is not a trivial task using classical force field methods that typically rely on point-charge models.Herein, a computational protocol capable of dealing with halogen bonds is presented. This protocol takes advantage of the addition of an off-center particle during the charge fitting procedure, and the resulting set of charges can be used along with the classical force field parameters from GAFF or GROMOS 54A7.