The Structure and Function of Mutant p53 Proteins

The tumor suppressor protein p53 (produced by the gene TP53) is implicated in over 50$% of human cancers.  Structural biology has made tremendous strides in recent years, particularly with the advent of protein modeling softwares such as AlphaFold.  Due to their unstable structures, p53 mutants have historically been difficult to model.  This study leverages AlphaFold to create the first complete models of p53 mutant proteins.  We show that it is possible to create highly accurate models of otherwise impossible to visualize mutant proteins using a computationally generated sequence library.  This has significant applications in the search for a cure for Li-Fraumeni Syndrome, the genetic disorder characterized by a TP53 mutation, and in the treatment of p53 related cancers.  With these structures, it is possible to develop new drugs for p53-based disease, marking a new frontier in personalized medicine in oncology.