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p53 Mutant Unfolds Faster Алика Паркс proposed an experiment to check if the mutant p53 unfolds faster than the normal one under weak stretching. On July 29, independent researcher Алика Паркс published a calculation and code for such an experiment. She suggests applying a constant weak force to a single molecule of mutant p53 and measuring how quickly the protein loses its folded form. p53 responds to DNA damage by stopping cell division to repair the genome or initiating cell death. p53 mutations are found in approximately half of tumors, with some making the DNA-binding domain of the protein less stable. In a 1997 study, several tumor variants of this domain were found to be less stable in solution than normal p53. The Y220C variant has a single amino acid substitution that creates a cavity on the surface of the protein, reducing its stability. In a 2008 study, small molecules were designed to bind to this cavity, increasing the temperature of melting and slowing down denaturation. Паркс proposes using this vulnerability differently: holding the protein under stretching until the less stable variant unfolds. According to Паркс' calculation, Y220C unfolds approximately 100 times faster than the normal domain under a constant force of 3-5 piconewtons. The difference in unfolding speeds translates into a difference in the fraction of unfolded molecules. 🔗 Read original →