Proteome-wide prediction of targets for aspirin: new insight into the molecular mechanism of aspirin

PeerJ

article

Shao-Xing Dai¹  Wen-Xing Li¹  Gong-Hua Li¹  Jing-Fei Huang¹ 

[1] State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences;Kunming College of Life Science, University of Chinese Academy of Sciences;Institute of Health Sciences, Anhui University;KIZ-SU Joint Laboratory of Animal Models and Drug Development, College of Pharmaceutical Sciences, Soochow University;Collaborative Innovation Center for Natural Products and Biological Drugs of Yunnan

关键词: Target;    Cancer;    Molecular docking;    Aspirin;    Cardiovascular disease;    Binding site;   

DOI  :  10.7717/peerj.1791

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Besides its anti-inflammatory, analgesic and anti-pyretic properties, aspirin is used for the prevention of cardiovascular disease and various types of cancer. The multiple activities of aspirin likely involve several molecular targets and pathways rather than a single target. Therefore, systematic identification of these targets of aspirin can help us understand the underlying mechanisms of the activities. In this study, we identified 23 putative targets of aspirin in the human proteome by using binding pocket similarity detecting tool combination with molecular docking, free energy calculation and pathway analysis. These targets have diverse folds and are derived from different protein family. However, they have similar aspirin-binding pockets. The binding free energy with aspirin for newly identified targets is comparable to that for the primary targets. Pathway analysis revealed that the targets were enriched in several pathways such as vascular endothelial growth factor (VEGF) signaling, Fc epsilon RI signaling and arachidonic acid metabolism, which are strongly involved in inflammation, cardiovascular disease and cancer. Therefore, the predicted target profile of aspirin suggests a new explanation for the disease prevention ability of aspirin. Our findings provide a new insight of aspirin and its efficacy of disease prevention in a systematic and global view.

【 授权许可】

CC BY