Effect of spatially distributed hydrophobic surface residues on protein-polymer association

The effect of the spatial distribution of hydrophobic surface residues on the adsorption of a weakly hydrophobic polymer to proteins has been examined using a coarse-grain model solved by Monte Carlo simulations. A given number of surface sites were distributed randomly on the protein surface subjected to a distance constraint. Five protein classes for which the minimum distance between the sites was 2, 3, 4, 5, and 6 Angstrom were considered, and for each class 10 proteins with different site distributions randomly generated were examined. As the strength of the hydrophobic interaction was increased, the onset of the polymer adsorption to the protein appeared first for proteins with a more heterogeneous site distribution. This holds both for the systematic variation of the site distribution for protein
of different classes and for the random variation among proteins within a class. The degree of heterogeneity of the site distributions was quantified using the variance of the number of sites located within randomly positioned circles placed on the protein surface. The conformational changes of the polymer at the adsorption were also studied.