Smoking-associated changes in serum TP53 levels and molecular characterization of nicotine interaction with the MDM2–p53 complex: an integrated clinical and in silico study

Smoking induces cellular stress and genomic damage that may disrupt regulation of the p53 tumor-suppressor pathway. This cross-sectional study evaluated serum p53 concentrations in 154 Iraqi adults, including 92 smokers and 62 non-smoking controls, and examined the predicted interaction of nicotine with the MDM2–p53 complex using molecular docking and molecular dynamics simulations. Serum p53 was measured by sandwich ELISA, while smokers were classified as Cigarette, narghile, or Electronic-Cigarette users, and associations between cumulative smoking exposure and serum p53 were assessed. Nicotine was docked into the MDM2–p53 peptide complex structure (PDB ID: 4HFZ) using MOE 2019, followed by a 110-ns molecular dynamics simulation in Desmond. Serum p53 concentrations were significantly higher in smokers than in controls (4791.2 vs. 3024.1 pg/mL, p < 0.001). No significant differences were detected among smoking types (p = 0.547), and cumulative exposure was not significantly correlated with serum p53 in any subgroup. Docking identified a preferred nicotine-binding pose with a predicted score of −5.31 kcal/mol and interactions involving Val28 and Arg29. The simulated complex exhibited marked early conformational adjustment, followed by a comparatively stable trajectory supported by persistent and intermittent noncovalent interactions. These findings indicate that smoking is associated with elevated circulating p53 concentrations and suggest that nicotine may interact with residues within the MDM2–p53 binding region; however, further cellular and biochemical validation is required.

Loại tài liệu:

Article - Bài báo

Tác giả:

Noor Kareem Khalifa

Đề mục:

Journal of Genetic Engineering and Biotechnology

Nhà xuất bản:

Elsevier

Ngày xuất bản:

September 2026

Số trang/ tờ:

Định dạng:

pdf

Định danh tư liệu:

DOI: https://doi.org/10.1016/j.jgeb.2026.100837 | ISSN 1687-157X

Nguồn gốc:

Journal of Genetic Engineering and Biotechnology, Volume 24, Issue 4, September 2026, 100837

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