title: Binding of charged ligands to macromolecules. Anomalous salt dependence.
abstract: Although interactions in biological systems occur in the presence of a large number of charged species, the binding of charged ligands to different biomolecules is often analyzed in a simplified model focusing only upon the receptor, ligand, and added salt. Here we demonstrate that the presence of charged macromolecules can affect binding to the receptor in an unexpected way. Experimental studies of the binding of barium ions to the chelator 5,5'-dibromo-1,2-bis(O-amino-phenoxy)-ethane-N,N,N',N'-tetraacetic acid in the presence of charged silica sols show that the binding affinity increases with added salt. The experimental findings are verified in Monte Carlo simulations using a dielectric continuum model with a uniform dielectric permittivity throughout the solution. The anomalous salt behavior is caused by a reduction of the chemical potential of the free ligand, which even in the absence of binding interacts strongly with the oppositely charged receptor. These results are also relevant for the interpretation of competition studies often used in the case of strong ligand binding.
authors.affiliation: Department of Theoretical Chemistry and Department of Biophysical Chemistry, Lund University, P.O. Box 124, S-22100 Lund, Sweden.
authors.forename: Fernando Luís B
authors.initials: FL
authors.lastname: da Silva
authors.forename: Sara
authors.initials: S
authors.lastname: Linse
authors.forename: Bo
authors.initials: B
authors.lastname: Jönsson
mesh_terms: D001464:Barium / Q000737:chemistry; D002614:Chelating Agents / Q000494:pharmacology; D002627:Chemistry, Physical / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D007477:Ions; D008024:Ligands; D046911:Macromolecular Substances / Q000737:chemistry*; D008956:Models, Chemical; D015233:Models, Statistical; D009010:Monte Carlo Method; D012492:Salts / Q000494:pharmacology*; D013816:Thermodynamics
chemical_list: D002614:Chelating Agents; D007477:Ions; D008024:Ligands; D046911:Macromolecular Substances; D012492:Salts; D001464:Barium