Fanconi anemia (FA) is a genetic disorder that occurs when certain genes responsible for repairing DNA replication and promoting homologous recombination fail to function properly. This leads to severe clinical symptoms and a wide range of cancer-related characteristics. Recent treatment approaches for FA involve hematopoietic stem cell transplantation (HSCT), which helps restore the population of stem cells. A survival study using p-values indicated that specific hub genes play a significant role in diagnosing and predicting the disease. To find potential medications that interact with the identified hub genes, researchers inferred drugs. Among hub genes, TP53 was found to be particularly promising through computational analysis. Further investigation focused on two drugs, Topiramate and Tocofersolan predicted based on drug bank database analysis. Molecular docking strategies were employed to assess the best binding pose of these drugs with TP53. Topiramate showed a binding affinity of -6.5 kcal/mol, while Tocofersolan showed -8.5 kcal/mol against the active residues within the binding pocket. Molecular dynamics (MD) simulations were conducted to observe the stability of each drug's interaction with the TP53 protein over time. Both drugs exhibited stable confirmation with only slight changes in the loop region of the TP53 protein during the simulation intervals. Results also shows that there was a high fluctuation observed during apo-sate simulation time intervals as compared to complex system. Hence, it is suggested that the exploration of structure-based drug design holds promising results to specific target. This could potentially lead to a breakthrough in future experimental approaches for FA treatment.Communicated by Ramaswamy H. Sarma.
Keywords: Biomarkers; TP53; binding energies; fanconi anemia; hub genes; molecular docking.