Binding of Charged Ligands to Macromolecules. Anomalous Salt Dependence

• Published in: The journal of physical chemistry. B Vol. 109; no. 5; pp. 2007 - 2013
• Main Authors: da Silva, Fernando Luís B, Linse, Sara, Jönsson, Bo
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 10-02-2005
• Subjects: Barium - chemistry; Chelating Agents - pharmacology; Chemical Sciences; Chemistry, Physical - methods; Dose-Response Relationship, Drug; Fysikalisk kemi; Hydrogen-Ion Concentration; Ions; Kemi; Ligands; Macromolecular Substances - chemistry; Models, Chemical; Models, Statistical; Monte Carlo Method; Natural Sciences; Naturvetenskap; Physical Chemistry; Salts - pharmacology; Teoretisk kemi; Theoretical Chemistry; Thermodynamics
• ISSN: 1520-6106; 1520-5207; 1520-5207
• DOI: 10.1021/jp049304o

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.