Structural simulation and selective inhibitor discovery study for histone demethylases KDM4E/6B from a computational perspective

This study focuses on two members of the lysine demethylase (KDM) family, KDM4E and KDM6B, which are significant in gene regulation and disease pathogenesis. KDM4E demonstrates selectivity for gene regulation, particularly concerning cancer, while KDM6B is implicated in inflammation and cancer. The study utilizes specific inhibitors, DA-24905 and GSK-J1, showcasing their exceptional selectivity for KDM4E and KDM6B, respectively. Employing an array of computational simulations, including sequence alignment, molecular docking, dynamics simulations, and free energy calculations, we conclude that although the binding cavities of KDM4E and KDM6B has high similarity, there are still some different crucial amino acid residues, indicating diverse binding forms between protein and ligands. Various interaction predominates when proteins are bound to different ligands, which also has significant effect on selective inhibition. These findings provide insights into potential therapeutic strategies for diseases by selectively targeting these KDM members.PMID:38636391 | DOI:10.1016/j.compbiolchem.2024.108072

Source: Computational Biology and Chemistry - April 18, 2024 Category: Bioinformatics Authors: Chenxiao Wang Baichun Hu Yi Yang Yihan Wang Juyue Qin Xiaolian Wen Yikuan Li Hui Li Yutong Wang Jian Wang Yang Liu Source Type: research