Journal Home > Volume 6 , Issue 1

Many efforts have been exerted toward screening potential drugs for targets, and conducting wet experiments remains a laborious and time-consuming approach. Artificial intelligence methods, such as Convolutional Neural Network (CNN), are widely used to facilitate new drug discovery. Owing to the structural limitations of CNN, features extracted from this method are local patterns that lack global information. However, global information extracted from the whole sequence and local patterns extracted from the special domain can influence the drug-target affinity. A fusion of global information and local patterns can construct neural network calculations closer to actual biological processes. This paper proposes a Fingerprint-embedding framework for Drug-Target binding Affinity prediction (FingerDTA), which uses CNN to extract local patterns and utilize fingerprints to characterize global information. These fingerprints are generated on the basis of the whole sequence of drugs or targets. Furthermore, FingerDTA achieves comparable performance on Davis and KIBA data sets. In the case study of screening potential drugs for the spike protein of the coronavirus disease 2019 (COVID-19), 7 of the top 10 drugs have been confirmed potential by literature. Ultimately, the docking experiment demonstrates that FingerDTA can find novel drug candidates for targets. All codes are available at http://lanproxy.biodwhu.cn:9099/mszjaas/FingerDTA.git.


menu
Abstract
Full text
Outline
About this article

FingerDTA: A Fingerprint-Embedding Framework for Drug-Target Binding Affinity Prediction

Show Author's information Xuekai Zhu1Juan Liu1( )Jian Zhang1Zhihui Yang1Feng Yang1Xiaolei Zhang1
School of Computer Science, Wuhan University, Wuhan 430072, China

Abstract

Many efforts have been exerted toward screening potential drugs for targets, and conducting wet experiments remains a laborious and time-consuming approach. Artificial intelligence methods, such as Convolutional Neural Network (CNN), are widely used to facilitate new drug discovery. Owing to the structural limitations of CNN, features extracted from this method are local patterns that lack global information. However, global information extracted from the whole sequence and local patterns extracted from the special domain can influence the drug-target affinity. A fusion of global information and local patterns can construct neural network calculations closer to actual biological processes. This paper proposes a Fingerprint-embedding framework for Drug-Target binding Affinity prediction (FingerDTA), which uses CNN to extract local patterns and utilize fingerprints to characterize global information. These fingerprints are generated on the basis of the whole sequence of drugs or targets. Furthermore, FingerDTA achieves comparable performance on Davis and KIBA data sets. In the case study of screening potential drugs for the spike protein of the coronavirus disease 2019 (COVID-19), 7 of the top 10 drugs have been confirmed potential by literature. Ultimately, the docking experiment demonstrates that FingerDTA can find novel drug candidates for targets. All codes are available at http://lanproxy.biodwhu.cn:9099/mszjaas/FingerDTA.git.

Keywords: fingerprint, drug-target binding affinity, new drug discovery

References(31)

[1]
D. C. Swinney and J. Anthony, How were new medicines discovered? Nat. Rev. Drug Discov., vol. 10, no. 7, pp. 507–519, 2011.
[2]
Y. Bao, K. Nakagawa, Z. Yang, M. Ikeda, K. Withanage, M. Ishigami-Yuasa, Y. Okuno, S. Hata, H. Nishina, and Y. Hata, A cell-based assay to screen stimulators of the hippo pathway reveals the inhibitory effect of dobutamine on the yap-dependent gene transcription, J. Biochem., vol. 150, no. 2, pp. 199–208, 2011.
[3]
Y. Wang, T. Yoshihara, S. King, T. Le, P. Leroy, X. Zhao, C. K. Chan, Z. H. Yan, and S. Menon, Automated high-throughput flow cytometry for high-content screening in antibody development, SLAS DISCOVERY Adv. Sci. Drug Discov., vol. 23, no. 7, pp. 656–666, 2018.
[4]
M. Keusgen, Biosensors: New approaches in drug discovery, Naturwissenschaften, vol. 89, no. 10, pp. 433–444, 2002.
[5]
S. Gupta, A. Jadaun, H. Kumar, U. Raj, P. K. Varadwaj, and A. R. Rao, Exploration of new drug-like inhibitors for serine/threonine protein phosphatase 5 of Plasmodium falciparum: A docking and simulation study, J. Biomol. Struct. Dyn., vol. 33, no. 11, pp. 2421–2441, 2015.
[6]
N. Rasool, A. Ashraf, M. Waseem, W. Hussain, and S. Mahmood, Computational exploration of antiviral activity of phytochemicals against NS2B/NS3 proteases from dengue virus, Turk. J. Biochem., vol. 44, no. 3, pp. 261–277, 2019.
[7]
K. Ghosh, S. A. Amin, S. Gayen, and T. Jha, Chemical-informatics approach to COVID-19 drug discovery: Exploration of important fragments and data mining based prediction of some hits from natural origins as main protease (Mpro) inhibitors, J. Mol. Struct., vol. 1224, p. 129026, 2021.
[8]
H. Öztürk, A. Özgür, and E. Ozkirimli, DeepDTA: Deep drug-target binding affinity prediction, Bioinformatics, vol. 34, no. 17, pp. i821–i829, 2018.
[9]
H. R. Rajpura and A. Ngom, Drug target interaction predictions using PU-leaming under different experimental setting for four formulations namely known drug target pair prediction, drug prediction, target prediction and unknown drug target pair prediction, in Proc. 2018 IEEE Conf. Computational Intelligence in Bioinformatics and Computational Biology, St. Louis, MO, USA, 2018, pp. 1–7.
[10]
L. Zhou, Z. Li, J. Yang, G. Tian, F. Liu, H. Wen, L. Peng, M. Chen, J. Xiang, and L. Peng, Revealing drug-target interactions with computational models and algorithms, Molecules, vol. 24, no. 9, p. 1714, 2019.
[11]
F. Hu, J. Jiang, and P. Yin, Interpretable prediction of protein-ligand interaction by convolutional neural network, in Proc. 2019 IEEE Int. Conf. Bioinformatics and Biomedicine, San Diego, CA, USA, pp. 656–659, 2019.
[12]
M. I. Davis, J. P. Hunt, S. Herrgard, P. Ciceri, L. M. Wodicka, G. Pallares, M. Hocker, D. K. Treiber, and P. P. Zarrinkar, Comprehensive analysis of kinase inhibitor selectivity, Nat. Biotechnol., vol. 29, no. 11, pp. 1046–1051, 2011.
[13]
J. Tang, A. Szwajda, S. Shakyawar, T. Xu, P. Hintsanen, K. Wennerberg, and T. Aittokallio, Making sense of large-scale kinase inhibitor bioactivity data sets: A comparative and integrative analysis, J. Chem. Inf. Model., vol. 54, no. 3, pp. 735–743, 2014.
[14]
Q. Zhao, F. Xiao, M. Yang, Y. Li, and J. Wang, AttentionDTA: Prediction of drug–target binding affinity using attention model, in Proc. 2019 IEEE Int. Conf. Bioinformatics and Biomedicine, San Diego, CA, USA, 2019, pp. 64–69.
[15]
D. Rogers and M. Hahn, Extended-connectivity fingerprints, J. Chem. Inf. Model., vol. 50, no. 5, pp. 742–754, 2010.
[16]
D. Weininger, SMILES, a chemical language and information system. 1. Introduction to methodology and encoding rules, J. Chem. Inf. Comput. Sci., vol. 28, no. 1, pp. 31–36, 1988.
[17]
RDKiT, https://www.rdkit.org/, 2021.
[18]
D. Weininger, A. Weininger, and J. L. Weininger, Smiles. 2. Algorithm for generation of unique SMILES notation, J. Chem. Inf. Comput. Sci., vol. 29, no. 2, pp. 97–101, 1989.
[19]
T. Mikolov, K. Chen, G. Corrado, and J. Dean, Efficient estimation of word representations in vector space, in Proc.1st Int. Conf. Learning Representations, Scottsdale, AZ, USA, 2013, p. 5043.
[20]
F. Pedregosa, G. Varoquaux, A. Gramfort, V. Michel, B. Thirion, O. Grisel, M. Blondel, P. Prettenhofer, R. Weiss, V. Dubourg, et al., Scikit-learn: Machine Learning in Python, J. Mach. Learn. Res., vol. 12, pp. 2825–2830, 2011.
[21]
T. Nguyen, H. Le, T. P. Quinn, T. Nguyen, T. D. Le, and S. Venkatesh, GraphDTA: Predicting drug–target binding affinity with graph neural networks, Bioinformatics, vol. 37, no. 8, pp. 1140–1147, 2021.
[22]
D. P. Kingma and J. Ba, Adam: A method for stochastic optimization, in Proc. 3rd Int. Conf. Learning Representations, San Diego, CA, USA, 2015.
[23]
V. Nada and M. Ljiljana, Gene similarity between hepatitis C virus and human proteins: A blood transfusion problem, Med. Pregl., vol. 58, nos. 11&12, pp. 582–586, 2005.
[24]
S. Feng and W. Wang, Bioactivities and structure–activity relationships of natural tetrahydroanthraquinone compounds: A review, Front. Pharmacol., vol. 11, p. 799, 2020.
[25]
J. Ding, J. Zhao, Z. Yang, L. Ma, Z. Mi, Y. Wu, J. Guo, J. Zhou, X. Li, Y. Guo, et al., Microbial natural product alternariol 5-O-methyl ether inhibits hiv-1 integration by blocking nuclear import of the pre-integration complex, Viruses, vol. 9, no. 5, p. 105, 2017.
[26]
Y. Kliger and E. Y. Levanon, Cloaked similarity between HIV-1 and SARS-CoV suggests an anti-SARS strategy, BMC Microbiol., vol. 3, p. 20, 2003.
[27]
R. J. Sydiskis, D. G. Owen, J. L. Lohr, K. H. Rosler, and R. N. Blomster, Inactivation of enveloped viruses by anthraquinones extracted from plants, Antimicrob. Agents Chemother., vol. 35, no. 12, pp. 2463–2466, 1991.
[28]
S. Das and A. Singha Roy, Naturally occurring anthraquinones as potential inhibitors of SARS-Cov-2 main protease: A molecular docking study, ChemRxiv preprint ChemRxiv: 12245270.v1, 2020.
[29]
H. Nakano, E. Kobayashi, I. Takahashi, T. Tamaoki, Y. Kuzuu, and H. Iba, Staurosporine inhibits tyrosine-specific protein kinase activity of Rous sarcoma virus transforming protein p60, J. Antibiot., vol. 40, no. 5, pp. 706–708, 1987.
[30]
B. Ellinger, D. Bojkova, A. Zaliani, J. Cinatl, C. Claussen, S. Westhaus, J. Reinshagen, M. Kuzikov, M. Wolf, G. Geisslinger, et al., Identification of inhibitors of SARS-Cov-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection, ResearchSquare preprint ResearchSquare: rs.3.rs-23951/v1, 2020.
[31]
Publication history
Copyright
Acknowledgements
Rights and permissions

Publication history

Received: 22 November 2021
Revised: 21 December 2021
Accepted: 16 February 2022
Published: 24 November 2022
Issue date: March 2023

Copyright

© The author(s) 2023.

Acknowledgements

This work was funded by the China National Key Research and Development Program (No. 2019YFA0904300). The authors thank the editors and the anonymous reviewers for their helpful comments and suggestions on the quality improvement of our present paper.

Rights and permissions

The articles published in this open access journal are distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).

Return