Prediction of mutant activity and its application in molecular design of tumor necrosis factor-alpha

Two models for prediction of the activity and stability of site-directed mutagenesis on tumor necrosis factor-alpha are established. The models are based on straightforward structural considerations, which do not require the elaboration of sitedirected mutagenesis on the protein core and the hydrophobic surface area by analyzing the pmperties of the mutated amino acid residues. The reliabilities of the models have been tested by analyzing the mutants of tumor necrosis factor-alpha (TNF-alpha) whose two leucine residues (L29, L157) were mutated. Based on these models, a TNFalpha mutant with high activity was created by molecular design.