NUDIX 水解酶 5 (NUDT5) 是一种参与与其他部分（例如 ADP-核糖）连接的核苷二磷酸水解的酶。该辅因子在氧化还原反应中至关重要，并且对于沉默调节蛋白和聚（ADP-核糖）聚合酶的活性至关重要，这些酶参与 DNA 修复和基因组稳定性。研究表明，NUDT5活性还可以影响NAD的稳态，从而影响癌细胞的代谢和存活。在这方面，NUDT5抑制剂的发现已成为癌症治疗的潜在治疗方法。在这项研究中，我们针对 NUDT5 酶对海洋细菌化合物进行了高通量虚拟筛选，并根据其对接分数选择了四种分子。这些化合物在 NUDT5 活性位点内建立了强大的相互作用，分子分析强调了 Trp28A 和 Trp46B 残基的关键作用。超过 200 ns 的分子动力学模拟表明行为稳定，均方根偏差值始终低于 3 Å，表明构象稳定性。自由能景观分析进一步支持了它们作为 NUDT5 抑制剂的潜力，为针对 NUDT5 相关乳腺癌的新型治疗策略提供了途径。© 2024。作者。

NUDIX hydrolase 5 (NUDT5) is an enzyme involved in the hydrolysis of nucleoside diphosphates linked to other moieties, such as ADP-ribose. This cofactor is vital in redox reactions and is essential for the activity of sirtuins and poly(ADP-ribose) polymerases, which are involved in DNA repair and genomic stability. It has been shown that NUDT5 activity can also influence NAD+ homeostasis, thereby affecting cancer cell metabolism and survival. In this regard, the discovery of NUDT5 inhibitors has emerged as a potential therapeutic approach in cancer treatment. In this study, we conducted a high-throughput virtual screening of marine bacterial compounds against the NUDT5 enzyme and four molecules were selected based on their docking scores. These compounds established strong interactions within the NUDT5 active site, with molecular analysis highlighting the key role of Trp28A and Trp46B residues. Molecular dynamics simulations over 200 ns indicated a stable behavior, in association with root mean square deviation values always below 3 Å, suggesting conformational stability. Free energy landscape analysis further supported their potential as NUDT5 inhibitors, offering avenues for novel therapeutic strategies against NUDT5-associated breast cancer.© 2024. The Author(s).