HOMOLOGY MODELING OF TRANSCRIPTIONAL REGULATORS: UNVEILING MECHANISMS AND DRUG DESIGN STRATEGIES IN LIVER CANCER RESEARCH
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Abstract
Background: Hepatocellular carcinoma (HCC) is a major cause of cancer-related morbidity and mortality worldwide. Transcriptional regulators play a key role in the development and progression of HCC by modulating critical pathways involved in cell cycle regulation, apoptosis, and metastasis. Understanding the structure and function of these regulatory proteins is essential for identifying potential therapeutic targets and developing novel treatments.
Objective: The aim of this study was to perform sequence and structural analysis of a hypothetical transcriptional regulator protein in HCC using homology modeling techniques. By constructing a reliable three-dimensional model of the protein, we sought to better understand its structural properties, potential interactions, and its role in liver cancer progression.
Materials: Homology modeling was conducted using Modeller 9.10. The sequence of the target protein was aligned with a suitable template identified through a BLAST search against the Protein Data Bank (PDB). The template with the highest sequence identity and best alignment was selected for model construction. Structural reliability was assessed using RMSD (Root Mean Square Deviation) and Ramachandran plot analysis to evaluate the quality and accuracy of the generated model.
Conclusion: The homology model of the transcriptional regulator in HCC revealed important structural insights that can contribute to understanding its role in liver cancer pathogenesis. The modeling approach showed that the protein’s structural integrity was satisfactory, with accurate phi and psi dihedral angles. Despite its potential, homology modeling has limitations, particularly when template quality is suboptimal. Validation through experimental data is necessary to confirm the model’s relevance for drug design and functional studies in HCC.
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Dr Sarwat Abbasi
MBBS, MPhil, Assistant Professor of Biochemistry, Ayub Medical College, Abbottabad, Pakistan
Dr. Nighat Parveen
MBBS, MPhil, Assistant Professor of Physiology, Abbottabad International Medical College, Abbottabad, Pakistan
Dr. Sumaira Javed
Associate Professor, Anatomy department, Ayub medical college, Abbottabad, Pakistan
Dr. Sofia Jadoon
MBBS, MPhil, Associate Professor, Anatomy, Abbottabad International Medical College, Abbottabad, Pakistan
Dr. Uzma Faryal
MBBS, MPhil, Professor of Biochemistry, Department of Biochemistry, Women Medical and Dental College, Abbottabad, Pakistan
Dr. Farnaz Iqbal Khan
Lecturer Anatomy, Abbottabad International Medical College, Abbottabad, Pakistan