Adsorption of proteins onto charged surfaces: A Monte Carlo approach with explicit ions

A computer model has been developed to simulate the adsorption of proteins onto charged surfaces displaying an electric double layer. Coadsorption of ions onto the surface is included by means of explicit ions. Only electrostatic interactions are considered. Monte Carlo simulations in the canonical ensemble of the enzyme cutinase and 15 variants (modeled from the X-ray tertiary structure of the wild-type) were performed. Adsorption free energies for all variants were calculated by the thermodynamic integration method. Distributions of the electric moment and the vector pointing toward the protein active site and parallel to its central β-sheet were determined to elucidate the mean orientation of the protein with respect to the surface as a function of its distance from the surface. It was found that the free energy of adsorption varied linearly with the total charge of the protein, while the electric moment (dipole moment) had a second-order but significant effect. Though an increase of the electric moment generally resulted in a slightly increased affinity of the protein for the surface, close to the surface the mean force acting on the protein clearly varied linearly with the strength of the electric moment, such that a clear correlation between the latter and the protein orientation with respect to the surface could be established. Wild-type cutinase displayed the highest affinity for the charged surface amongst all proteins having the same total charge, even though it did not have the largest electric moment. © 1996 by John Wiley & Sons, Inc.