Stabilization of hen egg white lysozyme by a cavity-filling mutation

Stabilization of a protein using cavity-filling strategy has hardly been su ccessful because of unfavorable van der Waals contacts. We succeeded in sta bilizing lysozymes by cavity-filling mutations. The mutations were checked by a simple energy minimization in advance. It was shown clearly that the s um of free energy change caused by the hydrophobicity and the cavity size w as correlated very well with protein stability. We also considered the arom atic-aromatic interaction. It is reconfirmed that the cavity-filling mutati on in a hydrophobic core is a very useful method to stabilize a protein whe n the mutation candidate is selected carefully.