ELECTROSTATIC AND VANDERWAALS CONTRIBUTIONS TO PROTEIN ADSORPTION - COMPUTATION OF EQUILIBRIUM-CONSTANTS

Although protein adsorption has been much described and exploited, lit tle effort has been directed toward the development of models for its a priori prediction. Here we describe a methodology that allows for th e computation of protein-surface equilibrium constants K(eq) (i.e., eq uilibria at low surface coverages) based on protein molecular structur e and surface properties. The crux of the model is the computation of the electrostatic and van der Waals energies of interaction between a colloidal protein molecule and a planar, charged surface at a fixed di stance from and orientation with respect to it. Results for the protei n lysozyme are presented; however, these calculations are computationa lly very time-intensive. Consequently, we utilize a simplified descrip tion of the protein as a low dielectric sphere with its net charge pla ced at the center. It is used in particular to compute the relationshi p, relevant to ion-exchange chromatography, between ionic strength and K(eq), due to the strong effect which salt exerts on electrostatic in teractions. The physical properties that affect the value of the equil ibrium constant are protein and surface net charges, Hamaker constant, and protein size; the first two influence electrostatic interactions, the third characterizes dispersion forces, and the last affects both types of interactions. In addition to allowing a priori prediction of adsorption equilibria, the construct presented in this paper can allow for improved understanding and interpretation of electrostatic and di spersive mechanisms for protein adsorption.