Machine-Learning-Enabled Virtual Screening for Inhibitors of Lysine-Specific Histone Demethylase 1

Molecules

卷:26

Tianwei Chen¹  Jiajun Zhou¹  Ziqi He¹  Shiying Wu¹  Yukun Lei¹  Bencan Tang¹  Jonathan D. Hirst²  Boon Giin Lee³ 

[1] Key Laboratory for Carbonaceous Waste Processing and Process Intensification Research of Zhejiang Province, University of Nottingham Ningbo China, 199 Taikang East Road, Ningbo 315100, China;

[2] School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK;

[3] School of Computer Science, University of Nottingham Ningbo China, 199 Taikang East Road, Ningbo 315100, China;

关键词: LSD1;    LSD1 inhibitors;    machine learning;    virtual screening;   

DOI  :  10.3390/molecules26247492

来源: DOAJ

【 摘 要 】

A machine learning approach has been applied to virtual screening for lysine specific demethylase 1 (LSD1) inhibitors. LSD1 is an important anti-cancer target. Machine learning models to predict activity were constructed using Morgan molecular fingerprints. The dataset, consisting of 931 molecules with LSD1 inhibition activity, was obtained from the ChEMBL database. An evaluation of several candidate algorithms on the main dataset revealed that the support vector regressor gave the best model, with a coefficient of determination ($R^2$) of 0.703. Virtual screening, using this model, identified five predicted potent inhibitors from the ZINC database comprising more than 300,000 molecules. The virtual screening recovered a known inhibitor, RN1, as well as four compounds where activity against LSD1 had not previously been suggested. Thus, we performed a machine-learning-enabled virtual screening of LSD1 inhibitors using only the structural information of the molecules.

【 授权许可】

Unknown