乳腺癌是全球妇女中最常见的癌症类型之一，其转移是导致死亡的重要原因。因此，识别参与乳腺癌转移的潜在蛋白抑制剂对于开发有效的治疗方案至关重要。BUB1丝氨酸/苏氨酸激酶B（BUB1B）是有丝分裂检查点控制的关键调节因子，该因子确保细胞分裂过程中染色体的正确分离。BUB1B的失调与多种人类疾病，包括乳腺癌相关。各种癌症类型中观察到了BUB1B的过度表达，并且已经显示其抑制剂能够导致癌细胞死亡。此外，BUB1B的抑制还被提出作为克服化疗和放疗抵抗性的潜在策略。考虑到BUB1B在细胞分裂中的重要性及其作为治疗靶点的潜力，开发BUB1B抑制剂一直是研究的焦点。尽管已经做出了一些努力，但目前仅少数BUB1B小分子抑制剂已被鉴定出来，强调了在此领域需要进一步研究的必要性。本研究旨在利用计算方法，从蘑菇活性化合物中发现BUB1B的潜在抑制剂，最终可能导致新的乳腺癌转移治疗方案的开发。本研究收集了文献中挑选的70种不同蘑菇的活性化合物，通过吸收、分布、代谢和排泄（ADME）特性来预测这些70种蘑菇化合物的药物样性，基于Lipinski的药物五性规则（RO5）。对这些活性化合物进行筛选，然后进行分子对接与BUB1B相互作用得出具有最佳构象结合亲和力的化合物。最好的两个复合物，即BUB1B-lepitaprocerin D和BUB1B-peptidoglycan，被用于分子动力学模拟。在蛋白质-配体复合物系统中，对这两个复合物进行了亲和力、稳定性和灵活性的评估。分子动力学（MD）模拟研究发现，lepitaprocerin D与BUB1B具有较好的能量有利的结合亲和力。结果显示，氨酸残基ASN123和SER157之间形成的氢键加强了lepitaprocerin D与BUB1B的亲和力。本研究确定了lepitaprocerin D作为BUB1B的潜在并且新颖的抑制剂，可能成为乳腺癌转移的潜在药物候选物，用于识别和控制乳腺癌转移的扩散。© 2023 作者姓名。IMR出版社发表。

Breast cancer is one of the most common types of cancer among women worldwide, and its metastasis is a significant cause of mortality. Therefore, identifying potential inhibitors of proteins involved in breast cancer metastasis is crucial for developing effective therapies. BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) is a key regulator of mitotic checkpoint control, which ensures the proper segregation of chromosomes during cell division. Dysregulation of BUB1B has been linked to a variety of human diseases, including breast cancer. Overexpression of BUB1B has been observed in various cancer types, and its inhibition has been shown to induce cancer cell death. Additionally, BUB1B inhibition has been suggested as a potential strategy for overcoming resistance to chemotherapy and radiation therapy. Given the importance of BUB1B in regulating cell division and its potential as a therapeutic target, the development of BUB1B inhibitors has been the focus of intense research efforts. Despite these efforts, few small molecule inhibitors of BUB1B have been identified, highlighting the need for further research in this area. In this study, the authors aimed to identify potential inhibitors of BUB1B from mushroom bioactive compounds using computational methods, which could ultimately lead to the development of new treatments for breast cancer metastasis.This study has incorporated 70 bioactive compounds (handpicked through literature mining) of distinct mushrooms that were considered and explored to identify a suitable drug candidate. Their absorption, distribution, metabolism and excretion (ADME) properties were obtained to predict the drug-likeness of these 70 mushroom compounds based on Lipinski's rule of 5 (RO5). Screening these bioactive compounds and subsequent molecular docking against BUB1B provided compounds with the best conformation-based binding affinity. The best two complexes, i.e., BUB1B-lepitaprocerin D and BUB1B-peptidoglycan, were subjected to molecular dynamic simulations. Both complexes were assessed for their affinity, stability, and flexibility in protein-ligand complex systems.The molecular dynamic (MD) simulation studies revealed that lepitaprocerin D has an energetically favorable binding affinity with BUB1B. Results showed that the formation of a hydrogen bond between residues ASN123 and SER157, and lepitaprocerin D had strengthened the affinity of lepitaprocerin D with BUB1B.This study identified lepitaprocerin D as a potential and novel inhibitor for BUB1B that could be a plausible drug candidate for identifying and controlling the spread of breast cancer metastasis.© 2023 The Author(s). Published by IMR Press.