MPD is commonly used to crystallize proteins for X-ray crystallography (see Crystallization). It is a relatively nonpolar molecule although soluble in water. It decreases the solubility of proteins because it is excluded from the solvent region around their surfaces by a strong repulsion between MPD and the electric charges of the ionized groups on the protein surface. The surface of a globular protein is a mosaic of many charges, and the charge density may be very high, even if the net charge on the protein is close to zero. MPD is repulsed by the charges and concentrates in the bulk solvent. The presence of MPD lowers the solubility of the protein. When the solubility limit of the protein is reached, it precipitates or crystallizes.
The exclusion of MPD from the surface of a protein results in preferential hydration of the protein, which would be expected to stabilize the protein folded conformation (see Stabilization And Destabilization By Co-Solvents). However, unfolding reduces the charge density on the protein molecule and, consequently, the repulsion of MPD. Furthermore, MPD interacts favorably with the nonpolar surfaces of proteins that are exposed upon unfolding. Consequently, MPD interacts more favorably with the unfolded state and actually destabilizes folded proteins. So it must be used with caution.
