Non-covalent conjugation of nanoparticles to antibodies via electrostatic interactions - A computational model

Conjugation of antibodies to nanoparticles is important for the development of vehicles with targeting specificity which can be used for diagnosis and treatment of cancer and other diseases. The antibody association with nanoliposomes and other nanoparticles is achieved mostly by generation of covalent bonds based on their chemical and structural properties. Here we describe a theoretical approach that may have implications for non-covalent conjugation of antibodies to nanoparticles based on their electrostatic properties. We analyzed in detail the crystal structure of the anti-HIV antibody Fab m18 and identified basic residues in the constant domain of the light chain. Some of these residues including four lysines at the positions 126, 183, 188, and 190, histidine 189 and agrinine 211 are highly exposed and form clusters. The electrostatic potential of the antibody surface was calculated by solving the Poisson-Boltzmann equation. The results suggest the existence of a dominant positively charged surface overlapping with the basic residues. We hypothesized that these conserved charges on the constant domain of antibody may facilitate binding to a negatively charged nanoparticle surface. Our computational analysis of the electrostatic energy of antibody-nanoparticle interactions provided evidence supporting this hypothesis and the possibility to design antibodies that can be non-covalently associated with nanoparticles via electrostatic interactions. These results may provide a framework for the development of novel approaches for the generation of antibody-nanoparticle conjugates.

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