Rearrangement of structure upon mutation must always compensate the loss of missing interactions.Eriksson have solved the crystal structures of mutants of T4 lysozyme containing mutations in the hydrophobic core.They have observed that the maximum changes in energy occur where the mutant has the full-sized empty cavity.As the cavity collapses because of neighboring side chains moving in, one observes correspondingly smaller changes in energy. It seems that the higher the packing density, the stronger the van der Waals interactions and also among the surrounding side chains, which are thus less likely to collapse into the cavity fromed upon mutation. As the hydrophobic interactions are cumulative, the effects of removing several methylene groups cause the largest decrease in stability.