Influence of Charged Groups on the Properties of Zwitterionic Moieties: A Molecular Simulation Study

Zwitterionic carboxybetaine and sulfobetaine materials have shown an excellent ability to resist nonspecific protein adsorption. It is desirable to obtain a better understanding of zwitterionic materials based on their molecular structures. This work aims to understand the roles of charged groups in zwitterionic moieties and to design new protein-resistant zwitterionic moieties beyond carboxybetaine and sulfobetaine. We conducted molecular simulations to study the hydration, self-association, and protein interactions of 12 zwitterionic moieties derived from three anionic groups (carboxylic, sulfonate, and sulfate) and four cationic groups (quaternary ammonium, tertiary ammonium, secondary ammonium, and primary ammonium). The partial charges of atoms in these moieties were obtained from quantum chemical calculations. Hydration was studied by evaluating the hydration free energy of moieties and the hydration structure and dynamics of the charged groups. All zwitterionic moieties have strong hydration, but their structural and dynamic properties depend on the types of cationic and anionic groups involved. The self-association and protein interactions of zwitterionic moieties also show relationships with the charged groups. Our simulation results indicate good protein-resistant ability of several zwitterionic moieties, one of which has also been shown by recent experiments.