In silico prediction and structural profiling of human CYP2E1 missense variants implicated in hepatotoxic injuries

CYP2E1 sits at the crossroads of xenobiotic metabolism and oxidative-stress generation, yet the functional consequences of most coding variants are unknown. We developed a structure-aware in silico pipeline to prioritize and mechanistically profile human CYP2E1 nsSNPs. From 490 missense SNPs collected, a consensus cascade of 27 prediction tools and evolutionary conservation filters yielded 24 high-confidence candidates, six highly conserved substitutions were subjected to all-atom MD. Trajectories analysis revealed variant-specific atomistic phenotypes spanning core collapse, access-tunnel rigidification, and localized electrostatic destabilization. G300R produced the largest structural disruption, while R359P induced pronounced rigidification of access-region dynamics, both emerged as top candidates for altered coupling efficiency and hepatotoxic risk. We provided a ranked variant list and mechanistic hypotheses linking coding substitutions to altered heme positioning and potential increases in ROS leakage. This structure-based prioritization framework is intended to guide experimental biochemical, cellular and pharmacogenetic follow-up in studies of drug-induced and chronic liver injury.

Loại tài liệu:

Article - Bài báo

Tác giả:

Soukaina Ettoury

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.2026.100799 | ISSN 1687-157X

Nguồn gốc:

Journal of Genetic Engineering and Biotechnology, Volume 24, Issue 4, September 2026, 100799

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