AiKPro: deep learning model for kinome-wide bioactivity profiling using structure-based sequence alignments and molecular 3D conformer ensemble descriptors

Machine Learning


  • Kobe, B. & Kemp, B. E. Principles of kinase regulation. Handb. Cell Signal. 2/e 2, 559–563 (2010).

    Article 

    Google Scholar 

  • Bhullar, K. S. et al. Kinase-targeted cancer therapies: Progress, challenges and future directions. Mol. Cancer 17, 1–20. https://doi.org/10.1186/s12943-018-0804-2 (2018).

    Article 
    CAS 

    Google Scholar 

  • Fagiani, F., Lanni, C., Racchi, M. & Govoni, S. Targeting dementias through cancer kinases inhibition. Alzheimer’s and dementia. Transl. Res. Clin. Interv. 6, e12044 (2020).

    Google Scholar 

  • Cohen, P., Cross, D. & Jänne, P. A. Kinase drug discovery 20 years after imatinib: Progress and future directions. Nat. Rev. Drug Discov. 20, 551–569 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Roskoski, R. Properties of FDA-approved small molecule protein kinase inhibitors: A 2023 update. Pharmacol. Res. 187, 106552 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ebied, A. M., Elmariah, H. & Cooper-DeHoff, R. M. New drugs approved in 2020. Am. J. Med. 134, 1096–1100 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ebied, A. M., Elmariah, H. & Cooper-DeHoff, R. M. New drugs approved in 2022. Am. J. Med. https://doi.org/10.1016/J.AMJMED.2023.02.019 (2023).

    Article 
    PubMed 

    Google Scholar 

  • Ebied, A. M., Elmariah, H. & Cooper-DeHoff, R. M. New drugs approved in 2021. Am. J. Med. 135, 836–839 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Li, Y. H. et al. The human kinome targeted by FDA approved multi-target drugs and combination products: A comparative study from the drug-target interaction network perspective. PLoS ONE 11, e0165737 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Csermely, P., Ágoston, V. & Pongor, S. The efficiency of multi-target drugs: The network approach might help drug design. Trends Pharmacol. Sci. 26, 178–182 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Harrison, C. Analysing kinase inhibitor selectivity. Nat. Rev. Drug Discov. 11, 21–21 (2012).

    Google Scholar 

  • White, P. T. & Cohen, M. S. The discovery and development of sorafenib for the treatment of thyroid cancer. Expert Opin. Drug Discov. 10, 427–439. https://doi.org/10.1517/17460441.2015.1006194 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Li, X. et al. Deep learning enhancing kinome-wide polypharmacology profiling: Model construction and experiment validation. J. Med. Chem. 63, 8723–8737 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bao, L. et al. Kinome-wide polypharmacology profiling of small molecules by multi-task graph isomorphism network approach. Acta Pharm. Sin. B 13, 54–67 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Li, Z. et al. KinomeX: A web application for predicting kinome-wide polypharmacology effect of small molecules. Bioinformatics 35, 5354–5356 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Abbasi, K. et al. DeepCDA: Deep cross-domain compound-protein affinity prediction through LSTM and convolutional neural networks. Bioinformatics 36, 4633–4642 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Merget, B., Turk, S., Eid, S., Rippmann, F. & Fulle, S. Profiling prediction of kinase inhibitors: Toward the virtual assay. J. Med. Chem. 60, 474–485 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • De Simone, G., Sardina, D. S., Gulotta, M. R. & Perricone, U. KUALA: A machine learning-driven framework for kinase inhibitors repositioning. Sci. Rep. 12, 1–16 (2022).

    Article 

    Google Scholar 

  • Ponzoni, I. et al. QSAR classification models for predicting the activity of inhibitors of beta-secretase (BACE1) associated with Alzheimer’s disease. Sci. Rep. 9, 1–13 (2019).

    Article 
    CAS 

    Google Scholar 

  • Blanco, J. L., Porto-Pazos, A. B., Pazos, A. & Fernandez-Lozano, C. Prediction of high anti-angiogenic activity peptides in silico using a generalized linear model and feature selection. Sci. Rep. 8, 1–11 (2018).

    Article 

    Google Scholar 

  • Ma, X. H. et al. Virtual screening of selective multitarget kinase inhibitors by combinatorial support vector machines. Mol. Pharm. 7, 1545–1560 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Jiang, Y. et al. Developing a Naïve Bayesian classification model with PI3Kγ structural features for virtual screening against PI3Kγ: Combining molecular docking and pharmacophore based on multiple PI3Kγ conformations. Eur. J. Med. Chem. 244, 114824 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hao, M., Li, Y., Wang, Y. & Zhang, S. Prediction of PKCθ inhibitory activity using the random forest algorithm. Int. J. Mol. Sci. 11, 3413–3433 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rohani, N. & Eslahchi, C. Drug–drug interaction predicting by neural network using integrated similarity. Sci. Rep. 9, 1–11 (2019).

    Article 
    CAS 

    Google Scholar 

  • Vijay, S. & Gujral, T. S. Non-linear deep neural network for rapid and accurate prediction of phenotypic responses to kinase inhibitors. iScience 23, 101129 (2020).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yang, M. et al. Machine learning models based on molecular fingerprints and an extreme gradient boosting method lead to the discovery of JAK2 inhibitors. J. Chem. Inf. Model 59, 5002–5012 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Born, J., Huynh, T., Stroobants, A., Cornell, W. D. & Manica, M. Active site sequence representations of human kinases outperform full sequence representations for affinity prediction and inhibitor generation: 3D effects in a 1D model. J. Chem. Inf. Model 62, 240–257 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Shim, J., Hong, Z.-Y., Sohn, I. & Hwang, C. Prediction of drug–target binding affinity using similarity-based convolutional neural network. Sci. Rep. 11, 4416 (2021).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lin, X.-Y. et al. Identification of pan-kinase-family inhibitors using graph convolutional networks to reveal family-sensitive pre-moieties. BMC Bioinform. 23, 247 (2022).

    Article 

    Google Scholar 

  • Sakai, M. et al. Prediction of pharmacological activities from chemical structures with graph convolutional neural networks. Sci. Rep. 11, 1–14 (2021).

    Article 
    ADS 

    Google Scholar 

  • Karimi, M., Wu, D., Wang, Z. & Shen, Y. DeepAffinity: Interpretable deep learning of compound–protein affinity through unified recurrent and convolutional neural networks. Bioinformatics 35, 3329–3338 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Deng, L., Zeng, Y., Liu, H., Liu, Z. & Liu, X. DeepMHADTA: Prediction of drug-target binding affinity using multi-head self-attention and convolutional neural network. Curr. Issues Mol. Biol. 44, 2287–2299 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Park, H., Brahma, R., Shin, J. M. & Cho, K. H. Prediction of human cytochrome P450 inhibition using bio-selectivity induced deep neural network. Bull. Korean Chem. Soc. 43, 261–269 (2022).

    Article 
    CAS 

    Google Scholar 

  • Lee, I., Keum, J. & Nam, H. DeepConv-DTI: Prediction of drug-target interactions via deep learning with convolution on protein sequences. PLoS Comput. Biol. 15, e1007129–e1007129 (2019).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Soh, J., Park, S. & Lee, H. HIDTI: Integration of heterogeneous information to predict drug-target interactions. Sci. Rep. 12, 1–12 (2022).

    Article 

    Google Scholar 

  • Li, Q. et al. PLA-MoRe: A protein-ligand binding affinity prediction model via comprehensive molecular representations. J. Chem. Inf. Model 62, 4380–4390 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Modi, V. & Dunbrack, R. L. A structurally-validated multiple sequence alignment of 497 human protein kinase domains. Sci. Rep. 9, 1–16 (2019).

    Article 
    CAS 

    Google Scholar 

  • Liu, T., Lin, Y., Wen, X., Jorissen, R. N. & Gilson, M. K. BindingDB: A web-accessible database of experimentally determined protein–ligand binding affinities. Nucleic Acids Res. 35, D198–D201 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Tanoli, Z. R. et al. Drug target commons 2.0: A community platform for systematic analysis of drug–target interaction profiles. Database 2018, 1–13 (2018).

    Article 
    PubMed 

    Google Scholar 

  • Metz, J. T. et al. Navigating the kinome. Nat. Chem. Biol. 7(4), 200–202 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Liu, T., Lin, Y., Wen, X., Jorissen, R. N. & Gilson, M. K. BindingDB: A web-accessible database of experimentally determined protein–ligand binding affinities. Nucleic Acids Res 35, D198–D201 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • RDKit. Preprint at https://www.rdkit.org/.

  • Ghose, A. K., Pritchett, A. & Crippen, G. M. Atomic physicochemical parameters for three dimensional structure directed quantitative structure-activity relationships III: Modeling hydrophobic interactions. J. Comput. Chem. 9, 80–90 (1988).

    Article 
    CAS 

    Google Scholar 

  • Lipinski, C. A., Lombardo, F., Dominy, B. W. & Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 46, 3–26 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Durant, J. L., Leland, B. A., Henry, D. R. & Nourse, J. G. Reoptimization of MDL keys for use in drug discovery. J. Chem. Inf. Comput. Sci. 42, 1273–1280 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Rogers, D. & Hahn, M. Extended-connectivity fingerprints. J. Chem. Inf. Model 50, 742–754 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Eberhardt, J., Santos-Martins, D., Tillack, A. F. & Forli, S. AutoDock Vina 1.2.0: New docking methods, expanded force field, and python bindings. J. Chem. Inf. Model 61, 3891–3898 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Xu, M., Shen, C., Yang, J., Wang, Q. & Huang, N. Systematic investigation of docking failures in large-scale structure-based virtual screening. ACS Omega 7, 39417–39428 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Forli, S. et al. Computational protein-ligand docking and virtual drug screening with the AutoDock suite. Nat. Protoc. 11, 905 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bland, J. M. & Altman, D. G. The odds ratio. BMJ 320, 1468 (2000).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Eid, S., Turk, S., Volkamer, A., Rippmann, F. & Fulle, S. Kinmap: A web-based tool for interactive navigation through human kinome data. BMC Bioinform. 18, 1–6 (2017).

    Article 

    Google Scholar 

  • Nguyen, N.-Q., Jang, G., Kim, H. & Kang, J. Perceiver CPI: A nested cross-attention network for compound–protein interaction prediction. Bioinformatics 39, btac731 (2023).

    Article 
    PubMed 

    Google Scholar 

  • Yang, Z., Zhong, W., Zhao, L. & Yu-Chian Chen, C. MGraphDTA: Deep multiscale graph neural network for explainable drug–target binding affinity prediction. Chem. Sci. 13, 816–833 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tang, J. et al. Making sense of large-scale kinase inhibitor bioactivity data sets: A comparative and integrative analysis. J. Chem. Inf. Model 54, 735–743 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Davis, M. I. et al. Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol. 29, 1046–1051 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Avram, S., Bora, A., Halip, L. & Curpan, R. Modeling kinase inhibition using highly confident data sets. J. Chem. Inf. Model 58, 957–967 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Chen, L. et al. TransformerCPI: Improving compound–protein interaction prediction by sequence-based deep learning with self-attention mechanism and label reversal experiments. Bioinformatics 36, 4406–4414 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hu, R., Xu, H., Jia, P. & Zhao, Z. KinaseMD: Kinase mutations and drug response database. Nucleic Acids Res. 49, D552–D561 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zhang, H. et al. An integrated deep learning and molecular dynamics simulation-based screening pipeline identifies inhibitors of a new cancer drug target TIPE2. Front Pharmacol. 12, 3297 (2021).

    Google Scholar 

  • Anwaar, M. U. et al. Combined deep learning and molecular docking simulations approach identifies potentially effective FDA approved drugs for repurposing against SARS-CoV-2. Comput. Biol. Med. 141, 105049 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lim, M. A., Yang, S., Mai, H. & Cheng, A. C. Exploring deep learning of quantum chemical properties for absorption, distribution, metabolism, and excretion predictions. J. Chem. Inf. Model 62, 6336–6341 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sun, Y., Jiao, Y., Shi, C. & Zhang, Y. Deep learning-based molecular dynamics simulation for structure-based drug design against SARS-CoV-2. Comput. Struct. Biotechnol. J. 20, 5014–5027 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Morrone, J. A., Weber, J. K., Huynh, T., Luo, H. & Cornell, W. D. Combining docking pose rank and structure with deep learning improves protein-ligand binding mode prediction over a baseline docking approach. J. Chem. Inf. Model 60, 4170–4179 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Rodríguez-Pérez, R., Miljković, F. & Bajorath, J. Assessing the information content of structural and protein-ligand interaction representations for the classification of kinase inhibitor binding modes via machine learning and active learning. J. Cheminform. 12, 1–14 (2020).

    Article 

    Google Scholar 

  • Xue, M. et al. Knowledge-based scoring functions in drug design. 1. Developing a target-specific method for kinase-ligand interactions. J. Chem. Inf. Model 50, 1378–1386 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Caffrey, D. R., Lunney, E. A. & Moshinsky, D. J. Prediction of specificity-determining residues for small-molecule kinase inhibitors. BMC Bioinform. 9, 1–15 (2008).

    Article 

    Google Scholar 

  • Lo, Y.-C. et al. Computational analysis of kinase inhibitor selectivity using structural knowledge. Bioinformatics 35, 235–242 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 



  • Source link

    Leave a Reply

    Your email address will not be published. Required fields are marked *