Bioinformatics
Saber Samadiafshar; Ali Nikakhtar; Sahel Samadiafshar; Nadia Garmsiri; Farnia Garmsiri; Roghayeh Azizi; Somayaeh - Farahmand
Volume 1, Issue 1 , March 2025, , Pages 11-16
Abstract
Background: Kidney renal clear cell carcinoma account for 2-3% of the global cancer burden and has the highest death rate of any genitourinary malignancy. Apoptosis is one of the natural immune cycles that fight against cancers. MicroRNAs are small non-coding RNA molecules that can influence the function ...
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Background: Kidney renal clear cell carcinoma account for 2-3% of the global cancer burden and has the highest death rate of any genitourinary malignancy. Apoptosis is one of the natural immune cycles that fight against cancers. MicroRNAs are small non-coding RNA molecules that can influence the function of proteins.Methods: The functional cycles of four microRNAs (133b, 155, 185, 217) involved in kidney cancer apoptosis were identified. Then, the effects of 7 selected medications which is routinely used by specialist doctors to treat cancer (Cabozantinib, Doxorubicin, Everolimus, Nelarabine, Sorafenib, Sunitinib, and Temsirolimus) on the target proteins were evaluated with dynamic techniques and molecular docking. Docking with powerful servers was evaluated in terms of the possibility of occurrence. Finally, the chemical and medicinal properties (Admet), toxicity, mutagenicity, and site of action of the selected drugs were predicted in silico.Results: The results indicated that drug Sunitinib had the best binding energy with 5 target proteins (VHL= -5, VEGF-A= -7.1, BACH1= -7.4, CUL4B= -5.1, JAK-2= -8 (kcal/mol)) and showed acceptable results in terms of molecular weight (398.5 Dalton), site of action (Mitochondria), and mutagenicity (0.5200 (negative)).Conclusion: The identified evidence demonstrates the positive efficacy and effectiveness of sunitinib in various kidney carcinomas. Targeted therapies are steps towards the targeted increase of apoptosis and the control of cell proliferation and migration, which enable the correct treatment of renal clear cell carcinoma and the prescribing of drugs that cause the least secondary damage to patients.
Bioinformatics
Somayeh Farahmand; Marzieh Dehghan Shasaltaneh; Faezeh Fatemi; Mahnaz Shojapour
Volume 1, Issue 1 , March 2025, , Pages 17-31
Abstract
Iron-rusticyanin reductase (Cyc2) is the first protein in the respiratory chain of Acidithiobacillus ferrooxidans (Af), which plays a crucial role in electron transfer. Cytochrome c (cytC) is located in the bacterial outer membrane (OM) and functions as the first electron carrier inside the respiratory ...
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Iron-rusticyanin reductase (Cyc2) is the first protein in the respiratory chain of Acidithiobacillus ferrooxidans (Af), which plays a crucial role in electron transfer. Cytochrome c (cytC) is located in the bacterial outer membrane (OM) and functions as the first electron carrier inside the respiratory ferrous iron oxidation pathway is encoded by the Cyc2 gene. The present computational research examines the effect of a novel Cyc2 mutation (F312Y) to enhance conformational flexibility of the mentioned protein for target recognition. Molecular dynamic simulations (MD) of wild and mutant types of Cyc2 protein were carried out. By analyzing RMSD, RMSF, SASA, Rg, H Bond, DSSP, PCA, ED, DCCM, FEL and EM the conformational variations of mutated protein were studied. The results of the RMSF analysis represent an increase in the flexibility of the ligand after mutant. Eventually, the flexibility of the active site probably improves electron transfer by increasing the amount of Eo at the mutation point. Our results confirm that the mutated protein retains its stability during the simulation. With the conversion of Phenylalanine 312 into Tyrosine, an alpha-amino acid with hydrophobic and nonpolar side chains changes to a polar side group with an extra -OH group. This resulted in more intracellular hydrogen bonds. Furthermore, the mutant variant was more stable than the wild-type. Findings from the present study indicate that an interface between the F312Y mutation and rusticyanin activation could improve the electron transfer rate and yield fruitful insight into site-specific mutagenesis studies.
