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

School of Computer Science, University of Nottingham Ningbo China, 199 Taikang East Road, Ningbo 315100, China

School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK

Authors to whom correspondence should be addressed.

Academic Editor: Jóhannes Reynisson

Molecules 2021, 26(24), 7492; https://doi.org/10.3390/molecules26247492

Received: 27 October 2021 / Revised: 5 December 2021 / Accepted: 6 December 2021 / Published: 10 December 2021

(This article belongs to the Special Issue Advances in Anticancer Drug Discovery II)

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Abstract

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. View Full-Text

Keywords: LSD1; LSD1 inhibitors; machine learning; virtual screening

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MDPI and ACS Style

Zhou, J.; Wu, S.; Lee, B.G.; Chen, T.; He, Z.; Lei, Y.; Tang, B.; Hirst, J.D. Machine-Learning-Enabled Virtual Screening for Inhibitors of Lysine-Specific Histone Demethylase 1. Molecules 2021, 26, 7492. https://doi.org/10.3390/molecules26247492

AMA Style

Zhou J, Wu S, Lee BG, Chen T, He Z, Lei Y, Tang B, Hirst JD. Machine-Learning-Enabled Virtual Screening for Inhibitors of Lysine-Specific Histone Demethylase 1. Molecules. 2021; 26(24):7492. https://doi.org/10.3390/molecules26247492

Chicago/Turabian Style

Zhou, Jiajun, Shiying Wu, Boon G. Lee, Tianwei Chen, Ziqi He, Yukun Lei, Bencan Tang, and Jonathan D. Hirst. 2021. "Machine-Learning-Enabled Virtual Screening for Inhibitors of Lysine-Specific Histone Demethylase 1" Molecules 26, no. 24: 7492. https://doi.org/10.3390/molecules26247492

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

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