Structure-Based Discovery of a Cryptic Druggable Pocket in TP53 C238Y: Implications for Targeted Therapy

Mutations in the TP53 gene are frequently found in many different types of human cancers These mutations interfere with important functions that normally prevent tumors, like controlling cell growth and causing programmed cell death. When TP53 can't do its job, cells start multiplying without control, and the cell's genetic material becomes unstable. Even though TP53 has long been known to be a key player in cancer it's been very difficult to develop drugs that target it. This is largely because of its flexible structure and the lack of clear binding sites for drugs. But, recent studies indicate that specific mutations can cause structural changes in TP53, creating new potential binding sites that could be useful for drug development. In this study, I used computer modeling and structural biological analysis to examine the c238y tp53 mutation . The results showed that this mutation dramatically reshapes the protein in the vicinity — it exposes a hidden pocket that could be a promising target for drugs. These results pave the way to conceptualising and designing therapies that are mutationally specific with the end goal being to disrupt or restore the default function of malfunctioning TP53 in cancer. This structural study lays the foundation for a follow-up phase involving virtual screening and drug-binding validation targeting the revealed cryptic pocket.