Other case

Thermostable enzymes, such as the thermostable triosephosphate isomerase form … have fewer internal cavities than their mesophilic counterparts, so that the removal of water trapped in internal cavities increase the entropy of the folded structure. Also, filling in cavities with larger residues will result in an unfolded polypeptide with a larger side chain to hydrate, lowering the entropy. Strategies devised to fill in internal cavities have been successful for subtilisin. In addition, thermostable enzymes often have shorter loops, leading to folded molecules that are more compact than their mesophilic counterparts and often have larger , more hydrophobic interfaces. This results in a smaller overall surface to be hydrated, leading to an increase in the entropy of the folded protein.

Shih have mutated a cluster of three buried residues in chicken lysozyme and have found three combinations that increase tis thermostability by 0.6 -1.3 kcal/mole. The crystal structure studies have indicated that one mutation(Ser91Thr) places the methyl group of threonine into a cavity in the protein and that another (Ill55Leu)improves the packing by moving some of the buried water molecules, of which there are four in a network, in this protein.

Structure of Chicken lysozyme showing residues 55 and 91

Hydrophobic Cavity of Chicken lysozyme