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Computational Design and Validation of a p53-SOG1 Hybrid Transcription Factor for Cancer Therapy and DNA Damage Response

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Bibliographic Details
Main Author:	Quazi, Uzaif
Format:	Recurso digital
Language:	English
Published:	Zenodo 2025
Subjects:	p53-SOG1 hybrid protein Hybrid transcription factor Synthetic transcription factors Cross-species DNA damage response Cancer therapy using hybrid proteins Tumor suppressor hybridization Computational protein design Molecular docking of transcription factors Molecular dynamics simulation of p53 DNA-binding efficiency in hybrid proteins Tetramerization of p53 hybrid Hybrid protein structural validation Synthetic biology and cancer therapeutics Bioinformatics in cancer drug development Protein engineering for tumor suppression In silico validation of transcription factors Functional validation of hybrid proteins Novel synthetic transcription factors Enhanced DNA-binding in hybrid p53 GROMACS simulation of DNA-binding proteins Computational approach to cancer treatment Protein hybridization for therapeutic applications p53 tumor suppressor engineering Molecular docking analysis of p53 hybrid Computational biology in cancer research Hybrid transcription factors in synthetic biology Structural modeling of DNA-binding proteins p53 and SOG1 fusion protein Protein stability analysis in hybrid molecules
Online Access:	Acceder al recurso
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_version_	1866902063199289344
author	Quazi, Uzaif
author_facet	Quazi, Uzaif
contents	<p>Understanding cross-species DNA damage response (DDR) regulators is critical <br>for advancing synthetic biology and cancer therapeutics. The tumor suppressor p53 <br>(mammalian) and SOG1 (plant-specific) share functional parallels in regulating <br>DDR, yet their hybridization remains unexplored. This study presents a novel <br>hypothesis: a p53-SOG1 hybrid protein can retain p53’s tumor suppressive <br>function while incorporating SOG1’s regulatory efficiency, potentially offering <br>new avenues for cancer therapy. <br>To test this hypothesis, we designed and computationally validated the hybrid <br>protein using molecular docking, molecular dynamics (MD) simulations, and <br>structural validation. Docking studies revealed enhanced DNA-binding affinity <br>(ZDOCK score: 1453), stable structural dynamics (RMSD: 0.11 nm), and high <br>hydration stability (SASA: 373 nm²). Hydrogen bonding (1200+ H-bonds) <br>stabilized DNA binding. MolProbity analysis positioned the hybrid in the 100th <br>percentile for structural accuracy. Notably, the hybrid retains p53’s tetramerization <br>via the oligomerization (OD) and C-terminal (CTD) domains. <br>Our findings provide strong in silico support for the feasibility of a p53-SOG1 <br>hybrid as a functional transcription factor. Future experimental directions include <br>expression in mammalian cells (HEK293T, HCT116), transcriptional activity <br>assays (qPCR, luciferase reporter), and DNA-binding kinetics via Surface Plasmon <br>Resonance (SPR). These steps will determine its viability for cancer therapeutics <br>and cross-species synthetic biology applications.</p>
format	Recurso digital
id	zenodo_https___doi_org_10_5281_zenodo_14956162
institution	Zenodo
language	eng
publishDate	2025
publisher	Zenodo
record_format	zenodo
spellingShingle	Computational Design and Validation of a p53-SOG1 Hybrid Transcription Factor for Cancer Therapy and DNA Damage Response Quazi, Uzaif p53-SOG1 hybrid protein Hybrid transcription factor Synthetic transcription factors Cross-species DNA damage response Cancer therapy using hybrid proteins Tumor suppressor hybridization Computational protein design Molecular docking of transcription factors Molecular dynamics simulation of p53 DNA-binding efficiency in hybrid proteins Tetramerization of p53 hybrid Hybrid protein structural validation Synthetic biology and cancer therapeutics Bioinformatics in cancer drug development Protein engineering for tumor suppression In silico validation of transcription factors Functional validation of hybrid proteins Novel synthetic transcription factors Enhanced DNA-binding in hybrid p53 GROMACS simulation of DNA-binding proteins Computational approach to cancer treatment Protein hybridization for therapeutic applications p53 tumor suppressor engineering Molecular docking analysis of p53 hybrid Computational biology in cancer research Hybrid transcription factors in synthetic biology Structural modeling of DNA-binding proteins p53 and SOG1 fusion protein Protein stability analysis in hybrid molecules <p>Understanding cross-species DNA damage response (DDR) regulators is critical <br>for advancing synthetic biology and cancer therapeutics. The tumor suppressor p53 <br>(mammalian) and SOG1 (plant-specific) share functional parallels in regulating <br>DDR, yet their hybridization remains unexplored. This study presents a novel <br>hypothesis: a p53-SOG1 hybrid protein can retain p53’s tumor suppressive <br>function while incorporating SOG1’s regulatory efficiency, potentially offering <br>new avenues for cancer therapy. <br>To test this hypothesis, we designed and computationally validated the hybrid <br>protein using molecular docking, molecular dynamics (MD) simulations, and <br>structural validation. Docking studies revealed enhanced DNA-binding affinity <br>(ZDOCK score: 1453), stable structural dynamics (RMSD: 0.11 nm), and high <br>hydration stability (SASA: 373 nm²). Hydrogen bonding (1200+ H-bonds) <br>stabilized DNA binding. MolProbity analysis positioned the hybrid in the 100th <br>percentile for structural accuracy. Notably, the hybrid retains p53’s tetramerization <br>via the oligomerization (OD) and C-terminal (CTD) domains. <br>Our findings provide strong in silico support for the feasibility of a p53-SOG1 <br>hybrid as a functional transcription factor. Future experimental directions include <br>expression in mammalian cells (HEK293T, HCT116), transcriptional activity <br>assays (qPCR, luciferase reporter), and DNA-binding kinetics via Surface Plasmon <br>Resonance (SPR). These steps will determine its viability for cancer therapeutics <br>and cross-species synthetic biology applications.</p>
title	Computational Design and Validation of a p53-SOG1 Hybrid Transcription Factor for Cancer Therapy and DNA Damage Response
topic	p53-SOG1 hybrid protein Hybrid transcription factor Synthetic transcription factors Cross-species DNA damage response Cancer therapy using hybrid proteins Tumor suppressor hybridization Computational protein design Molecular docking of transcription factors Molecular dynamics simulation of p53 DNA-binding efficiency in hybrid proteins Tetramerization of p53 hybrid Hybrid protein structural validation Synthetic biology and cancer therapeutics Bioinformatics in cancer drug development Protein engineering for tumor suppression In silico validation of transcription factors Functional validation of hybrid proteins Novel synthetic transcription factors Enhanced DNA-binding in hybrid p53 GROMACS simulation of DNA-binding proteins Computational approach to cancer treatment Protein hybridization for therapeutic applications p53 tumor suppressor engineering Molecular docking analysis of p53 hybrid Computational biology in cancer research Hybrid transcription factors in synthetic biology Structural modeling of DNA-binding proteins p53 and SOG1 fusion protein Protein stability analysis in hybrid molecules
url	https://doi.org/10.5281/zenodo.14956162