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المؤلفMuhammad, Suleman
المؤلفKhattak, Aishma
المؤلفAkbar, Fazal
المؤلفRizwan, Muhammad
المؤلفTayyab, Muhammad
المؤلفYousaf, Muhammad
المؤلفKhan, Abbas
المؤلفAlbekairi, Norah A.
المؤلفAgouni, Abdelali
المؤلفCrovella, Sergio
تاريخ الإتاحة2024-01-28T10:33:56Z
تاريخ النشر2024-03-31
اسم المنشورInternational Journal of Biological Macromolecules
المعرّفhttp://dx.doi.org/10.1016/j.ijbiomac.2024.129559
الرقم المعياري الدولي للكتاب01418130
معرّف المصادر الموحدhttps://www.sciencedirect.com/science/article/pii/S0141813024003623
معرّف المصادر الموحدhttp://hdl.handle.net/10576/51236
الملخصCancer is a medical condition that is caused by the abnormal growth and division of cells, leading to the formation of tumors. The E2F1 and RB pathways are critical in regulating cell cycle, and their dysregulation can contribute to the development of cancer. In this study, we analyzed experimentally reported SNPs in E2F1 and assessed their effects on the binding affinity with RB. Out of 46, nine mutations were predicted as deleterious, and further analysis revealed four highly destabilizing mutations (L206W, R232C, I254T, A267T) that significantly altered the protein structure. Molecular docking of wild-type and mutant E2F1 with RB revealed a docking score of −242 kcal/mol for wild-type, while the mutant complexes had scores ranging from −217 to −220 kcal/mol. Molecular simulation analysis revealed variations in the dynamics features of both mutant and wild-type complexes due to the acquired mutations. Furthermore, the total binding free energy for the wild-type E2F1-RB complex was −64.89 kcal/mol, while those of the L206W, R232C, I254T, and A267T E2F1-RB mutants were −45.90 kcal/mol, −53.52 kcal/mol, −55.67 kcal/mol, and −61.22 kcal/mol, respectively. Our study is the first to extensively analyze E2F1 gene mutations and identifies candidate mutations for further validation and potential targeting for cancer therapeutics.
راعي المشروعThis work was supported by Qatar University grant No. QUPD-CAS-23-24-491.
اللغةen
الناشرElsevier
الموضوعE2F1
SNPs
Molecular simulation
العنوانAnalysis of E2F1 single-nucleotide polymorphisms reveals deleterious non-synonymous substitutions that disrupt E2F1-RB protein interaction in cancer
النوعArticle
رقم المجلد260
dc.accessType Full Text


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