摘要
自分泌运动因子(ATX)在心血管疾病、炎症和肿瘤的病理过程中发挥重要作用。对具有抑制ATX活性的吲哚类化合物进行了三维定量构效关系(3D-QSAR)和分子对接研究。采用CoMFA和CoMSIA模型对40个ATX抑制剂构建3D-QSAR模型,阐明了抑制剂结构与生物活性之间的关系,同时利用Surflex-Dock进行分子对接,研究该类化合物与ATX蛋白的结合模式。CoMFA模型(q^(2)=0.668,r^(2)=0.992)和CoMSIA模型(q^(2)=0.727,r^(2)=0.988)表明其具有良好的预测能力和机制可解释能力,分子对接表明上述化合物与ATX均能很好地结合,Ser306、Glu232和His121是影响上述化合物与ATX结合的主要氨基酸残基。本研究为进一步设计合成ATX抑制剂提供理论依据,对开发高效ATX抑制剂具有指导意义。
Autotoxin(ATX)plays an important role in the pathological processes of cardiovascular diseases,inflammation and tumors.In this study,indole compounds with ATX inhibitory activity are studied by three-dimensional quantitative structure-activity relationship(3D-QSAR)and molecular docking.3D-QSAR models of 40 ATX inhibitors are built by using CoMFA and CoMSIA models to clarify the relationship between the structure of inhibitors and their biological activities.Surflex-Dock is employed for molecular docking to study the binding mode of these compounds with ATX protein.The CoMFA model(q^(2)=0.668,r^(2)=0.992)and CoMSIA model(q^(2)=0.727,r^(2)=0.988)shows they have good predictive ability and mechanism interpretation ability.Molecular docking shows the above compounds bind ATX well.Ser306,Glu232,and His121 are the main amino acid residues that affect the binding of the above compounds with ATX.Our study may provide some insights for the further design and synthesis of ATX inhibitors as well as the development of efficient ATX inhibitors.
作者
沈燕
潘亮
刘燕
李雪梅
秦菊梅
赵学敏
SHEN Yan;PAN Liang;LIU Yan;LI Xuemei;QIN Jumei;ZHAO Xuemin(School of Pharmacy and Bioengineering,Chongqing University of Technology,Chongqing 400054,China)
出处
《重庆理工大学学报（自然科学）》
CAS
北大核心
2024年第8期272-280,共9页
Journal of Chongqing University of Technology：Natural Science
基金
重庆市自然科学基金项目(CSTB2022NSCQ-MSX1493)。
关键词
自分泌运动因子
抑制剂
三维定量构效关系
分子对接
构效关系
autotoxin
inhibitors
three-dimensional quantitative structure-activity relationship
molecular docking
structure activity relationship
