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针对p53-MDMX相互作用的新型小分子的基于计算的药物设计

Abel Ujaigbe Egbemhenghe¹, Olajide Enoch Aderemi², Bamidele Samson Omotara²

¹Department of Chemistry and Biochemistry, Texas Technology University, Lubbock, TX, USA.

Journal of biomolecular structure & dynamics

|August 14, 2023

概括

计算方法确定了三种抑制MDMX-p53相互作用的小分子. 这些化合物表现出稳定的结合和强键,具有作为针对p53瘤抑制路径的新抗癌剂的潜力.

科学领域:

生物化学生化学
分子生物学分子生物学
药理学药理学是指药理学的学科.

背景情况:

抑制p53瘤通路对于预防癌症至关重要.
对MDM2 (Murine双分钟2) 和MDMX (Murine双分钟X) 蛋白质的失调会影响p53的稳定性.
过度表达MDMX可以导致p53降解,促进癌症的发展.

研究的目的:

为了确定MDMX-p53相互作用的新型小分子抑制剂.
评估潜在抑制剂与MDMX的结合稳定性和相互作用.

主要方法:

利用药模拟和分子对接来选PubChem数据库.
进行了10万 psi的分子动力学模拟.
使用根平均平方偏差 (RMSD) 和根平均平方波动 (RMSF) 评估结合稳定性.
分析了分子间键 (HBOND) 相互作用.

主要成果:

已经确定了三种潜在的MDMX-p53抑制剂:CID_25094615,CID_137634453和CID_25094344.
所有已识别的化合物都表现出与MDMX的稳定结合.
化合物与对照配体相比显示较低的RMSD和RMSF值,这表明其稳定性优越.
在候选抑制剂中观察到更强的分子间HBOND相互作用.

结论:

这些已识别的化合物是抗癌药物开发的有希望的主要候选物.
针对MDMX-p53相互作用为MDMX过度表达的癌症提供了可行的治疗策略.
这些抑制剂显示出稳定p53和恢复其瘤抑制功能的潜力.

关键词:

癌症治疗疗法癌症治疗发现药物的发现.分子对接的分子对接.分子动力学分子动力学 p53-MDMX 在线播放

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