Abstract
Deep learning algorithms can be used to improve the efficiency of drug design, which is a very meaningful research topic. This paper proposes a targeted drug design model based on the gated recurrent unit (GRU) neural network algorithm, which trains a large number of drug molecules obtained from the Chembl database for generating a generic and unbiased molecular library. For improving the efficiency and accuracy of the trained model, a fine-tuning strategy is used to train against the active compounds of the target protein. In addition, a TopP sampling strategy is used to sample molecular tokens for reducing the number of generated drug molecules that are invalid or existing drug molecules. Finally, the novel coronavirus 3CLpro protease is selected for verifying the effectiveness of the proposed model. Molecular docking results show that the molecules generated by the proposed model have lower average binding energies than the existing active compounds.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Okea, A., Sahin, D., Chen, X., Shang, Y.: High throughput screening for drug discovery and virus detection. Comb. Chem. High Throughput Screen. 25(9), 1518–1533 (2021)
Evanthia, L., George, S., Demetrios, V., Zoe, C.: Structure-based virtual screening for drug discovery: principles, applications and recent advances. Current Top. Med. Chem. 14(16), 1923–1938 (2014)
Hartenfeller, M., Proschak, E., Andreas Schüller, Schneider, G.: Concept of combinatorial de novo design of drug-like molecules by particle swarm optimization. Chem. Biol. Drug Des. 72(1), 16–26 (2010)
Cwla, B., Ys, C., Yd, D., Uy, E.: Asrnn: a recurrent neural network with an attention model for sequence labelling–science direct. Knowl.-Based Syst. 212, 106548 (2021)
Goodfellow, I., et al.: Generative adversarial nets. Neural Inf. Process. Syst. 2(14), 2672–2680 (2014)
Gómez-Bombarelli, R., et al.: Automatic chemical design using a data-driven continuous representation of molecules. ACS Cent. Sci. 4, 268–276 (2018)
Wu, J., Hu, C., Wang, Y., Hu, X., Zhu, J.: A hierarchical recurrent neural network for symbolic melody generation. IEEE Trans. Cybern. 50(6), 2749–2757 (2020)
Fabio, B., Marcello, F., Riccardo, S.: On the stability properties of gated recurrent units neural networks. Syst. Control Lett. 157 (2021)
Pan, X.: De novo molecular design of caspase-6 inhibitors by a gru-based recurrent neural network combined with a transfer learning approach. Pharmaceuticals 14(12), 1249 (2021)
Morris, G.M., et al.: AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J. Comput. Chem. 30(16), 2785–2791 (2009)
Lin, X.L., Zhang, X.L.: Prediction of hot regions in PPIs based on improved local community structure detecting. IEEE/ACM Trans. Comput. Biol. Bioinform. 15(5), 1470–1479 (2018)
Zhang, X.L., Lin X.L., et al.: Efficiently predicting hot spots in PPIs by combining random forest and synthetic minority over-sampling technique. IEEE/ACM Trans. Comput. Biol. Bioinform. 16(3), 774–781 (2019)
Lin, X.L., Zhang, X.L., Xu, X.: Efficient classification of Hot spots and Hub protein interfaces by recursive feature elimination and gradient boosting. IEEE/ACM Trans. Comput. Biol. Bioinform. 17(5), 1525–1534 (2020)
Behzadipour, Y., Gholampour, M., Pirhadi, S.: Viral 3CLpro as a target for antiviral intervention using milk-derived bioactive peptides. Int. J. Pept. Res. Ther. 27, 2703–2716 (2021)
Gupta, A., Müller, A.T., Huisman, B., Fuchs, J.A., Schneider, P., Schneider, G.: Generative recurrent networks for de novo drug design. Mol. Inform. 37(1–2), 1700111 (2018)
Jeon, S., Ko, M., Lee, J., Choi, I., Kim, S.: Identification of antiviral drug candidates against sars-cov-2 from fda-approved drugs. Antimicrob. Agents Chemother. 64(7) (2020)
Weston, S., et al.: Broad anti-coronavirus activity of food and drug administration-approved drugs against sars-cov-2 in vitro and sars-cov in vivo. J. Virol. 94(21), e01218-e1220 (2020)
Touret, F., et al.: In vitro screening of a fda approved chemical library reveals potential inhibitors of sars-cov-2 replication. Sci. Rep. 10(1), 13093 (2020)
Fintelman-Rodrigues, N., et al.: Atazanavir, alone or in combination with ritonavir, inhibits sars-cov-2 replication and proinflammatory cytokine production. Antimicrob. Agents Chemother. 64(10), e00825–20 (2020)
Yamamoto, N., Matsuyama, S., Hoshino, T., Yamamoto, N.: Nelfinavir inhibits replication of severe acute respiratory syndrome coronavirus 2 in vitro. bio Rxiv (2020). https://doi.org/10.1101/2020.04.06.026476
Riva, L., Yuan, S., Yin, X., et al.: Discovery of sars-cov-2 antiviral drugs through large-scale compound repurposing. Nature 586, 113–119 (2020)
Janes, J., et al.: The reframe library as a comprehensive drug repurposing library and its application to the treatment of cryptosporidiosis. Proc. Natl. Acad. Sci. U.S.A. 115(42), 10750–10755 (2018)
Wang, S., Sun, Q., Xu, Y., Pei, J., Lai, L.: A transferable deep learning approach to fast screen potential antiviral drugs against sars-cov-2. Brief. Bioinform. 22(6), bbab211 (2021)
Santana, M.V.S., Silva-Jr, F.P.: De novo design and bioactivity prediction of sars-cov-2 main protease inhibitors using recurrent neural network-based transfer learning. BMC Chem. 15(1), 8 (2021)
Popova, M., Isayev, O., Tropsha, A.: Deep reinforcement learning for de-novo drug design. Sci. Adv. 4(7), eaap7885 (2018)
Chenthamarakshan, V., et al.: Cogmol: target-specific and selective drug design for COVID-19 using deep generative models (2020)
Yasonik, J.: Multiobjective de novo drug design with recurrent neural networks and nondominated sorting. J. Cheminform. 12(1), 1–9 (2020). https://doi.org/10.1186/s13321-020-00419-6
Wei, X., et al.: Botanical drugs: a new strategy for structure-based target prediction. Brief. Bioinform. 23(1), bbab425 (2022)
Acknowledgements
The authors thank the members of Machine Learning and Artificial Intelligence Laboratory, School of Computer Science and Technology, Wuhan University of Science and Technology, for their helpful discussion within seminars. This work was supported by National Natural Science Foundation of China (No. 61972299, 61502356).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this paper
Cite this paper
Tao, J., Zhang, X., Lin, X. (2022). A Targeted Drug Design Method Based on GRU and TopP Sampling Strategies. In: Huang, DS., Jo, KH., Jing, J., Premaratne, P., Bevilacqua, V., Hussain, A. (eds) Intelligent Computing Theories and Application. ICIC 2022. Lecture Notes in Computer Science, vol 13394. Springer, Cham. https://doi.org/10.1007/978-3-031-13829-4_37
Download citation
DOI: https://doi.org/10.1007/978-3-031-13829-4_37
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-13828-7
Online ISBN: 978-3-031-13829-4
eBook Packages: Computer ScienceComputer Science (R0)