Design and in silico characterization of a novel chimeric P53-SOG1 fusion protein for enhanced dna damage response and tumor suppression.

The tumor suppressor p53 plays an essential role in preserving genomic stability through DNA damage response (DDR) and apoptosis in mammalian systems. By comparison, the transcription factor SOG1 (SUPPRESSOR OF GAMMA RESPONSE 1) is the main regulator of DDR in plants but has similar mechanisms to those occupied by p53 in humans. In this current study, we have designed and through computational characterization of a novel chimeric fusion protein composed of human p53 and the NAC domain of SOG1 from Arabidopsis thaliana, which was meant to increase the efficacy of DDR and apoptosis signaling. The fusion protein, a total of 336 amino acids and a molecular weight of 37.6 kDa, was modeled through protein-protein docking approaches with ClusPro and HDOCK, followed by molecular dynamics (MD) simulations of 100 ns to measure its stability, flexibility, and potential interactions with protein partners. The hybrid protein showed a favorable binding free energy with important regulatory partners MDM2 and BRCA1 (BRCT domain), and docked favorably with DNA (PDB ID: 1TUP), demonstrating that DNA-binding capability remained intact. This study proposes a new strategy for treating cancer and also expands the medicinal use of this study by describing, for the first time, the direct fusion of plant and animal protein, providing a new avenue for cross-kingdom therapeutic protein engineering.