ADSORPTION OF PROTEINS ONTO CHARGED SURFACES - A MONTE-CARLO APPROACHWITH EXPLICIT IONS

A computer model has been developed to simulate the adsorption of prot eins onto-charged surfaces displaying an electric double layer. Coadso rption of ions onto the surface is included by means of explicit ions. Only electrostatic interactions are considered. Monte Carlo simulatio ns in the canonical ensemble of the enzyme cutinase and 15 variants (m odeled from the X-ray tertiary structure of the wild-type) were perfor med. 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 t o its central beta-sheet were determined to elucidate the mean orienta tion of the protein with respect to the surface as a function of its d istance from the surface. It was found that the free energy of adsorpt ion varied linearly with the total charge of the protein, while the el ectric moment (dipole moment) had a second-order but significant effec t. Though an increase of the electric moment generally resulted in a s lightly increased affinity of the protein for the surface, close to th e surface the mean force acting on the protein clearly varied linearly with the strength of the electric moment, such that a clear correlati on 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 . (C) 1996 by John Wiley & Sons, Inc.