PREDICTION OF MUTANT ACTIVITY AND ITS APPLICATION IN MOLECULAR DESIGNOF TUMOR-NECROSIS-FACTOR-ALPHA

Two models for prediction of the activity and stability of site-direct ed mutagenesis on tumor necrosis factor-a are established. The models are based on straightforward structural considerations, which do nor r equire the elaboration of site-directed mutagenesis on the protein cor e and the hydrophobic surface area by analyzing the properties of the mutated amino acid residues. The reliabilities of the models have been tested by analyzing the mutants of tumor necrosis factor-alpha (TNF-a lpha) whose two leucine residues (L29, L157) were mutated. Based on th ese models, a TNF-alpha mutant with high activity was created by molec ular design.