Solvent interactions with proteins are well known to be among the most important driving forces in protein folding and unfolding. In line with this view, growing evidence suggests that PEGylation enhances the thermal stability of conjugated proteins by modifying the solvation network surrounding the protein and altering its solvent-accessible surface area (SASA). Computational simulations with PEGylated polypeptides and small proteins observed that PEGylation-drive increase in protein stability correlated with a reduction in SASA. A combined experimental and computational study of a PEGylated small protein Pin1 indicated that PEGylation increased the disorder of water molecules in the protein solvation shell. Coupled to this question is the related question of the extent of interaction between the protein and polymer and how the two are spatially organized. In general, two models are frequently invoked to describe PEG-protein interactions: the "dumbbell model" and the "shroud model." These models differ in the extent of interaction between the protein and conjugated polymer. In the dumbbell model, the protein and covalently attached PEG remain loosely connected and behave as largely independent molecules.