MODELING OF PROTEIN ADSORPTION ON POLYMER SURFACES - COMPUTATION OF ADSORPTION POTENTIAL

This work is based on a model developed to understand and predict the retention behavior of proteins in ion-exchange chromatography. The ads orption of two types of proteins is studied: a calcium-binding acidic protein, the alpha-lactalbumin (ALC) and a basic protein, the hen egg white lysozyme (HEWL). Their model structures are taken from the prote in data bank, and the poly(vinylimidazole) polymer structure is built and used as the model stationary phase. To calculate the interactions between the protein and the polymeric stationary phase, the model expl icitly considers all of the atoms. A set of parameters obtained from t he AMBER force field is assigned to each of them, and the point charge s on the polymer atoms are calculated on a semiempirical basis. The so lvent effect is taken into account by introducing in the calculations a Linear dependence of the dielectric permittivity on the separation d istance. Protein/polymer interaction energies are evaluated for 2592 c onfigurations scanning the whole space of possible orientations from t he bulk down to the contact with the adsorbent. We are able to reprodu ce the difference in retention between calcium-loaded and -depleted AL C; HEWL is repelled from the surface in agreement with its elution as a nonretained compound. Preferred orientations are found for each of t he model proteins that allow the determination of the residues involve d in the interaction with the anion-exchanger support. Moreover, we ca lculate an average effective net charge of the proteins.