In Silico drug repurposing pipeline using deep learning and structure based approaches in epilepsy

Beghi, E. The epidemiology of epilepsy. Neuroepidemiology 54, 185–191 (2020).Article 
PubMed 

Google Scholar 
Fiest, K. M. et al. Prevalence and incidence of epilepsy: A systematic review and meta-analysis of international studies. Neurology 88, 296–303 (2017).Article 
PubMed 
PubMed Central 

Google Scholar 
Goldenberg, M. M. Overview of drugs used for epilepsy and seizures: etiology, diagnosis, and treatment. P T Peer-Rev. J. Formul. Manag. 35, 392–415 (2010).
Google Scholar 
Dyńka, D., Kowalcze, K. & Paziewska, A. The role of ketogenic diet in the treatment of neurological diseases. Nutrients 14, 5003 (2022).Article 
PubMed 
PubMed Central 

Google Scholar 
Rugg-Gunn, F., Miserocchi, A. & McEvoy, A. Epilepsy surgery. Pract. Neurol. 20, 4–14 (2020).PubMed 

Google Scholar 
Ryvlin, P., Rheims, S., Hirsch, L. J., Sokolov, A. & Jehi, L. Neuromodulation in epilepsy: state-of-the-art approved therapies. Lancet Neurol. 20, 1038–1047 (2021).Article 
PubMed 

Google Scholar 
Ko, Y., Lee, C., Lee, Y. & Lee, J.-S. Systematic approach for drug repositioning of anti-epileptic drugs. Diagn. Basel Switz. 9, 208 (2019).CAS 

Google Scholar 
Nevitt, S. J., Sudell, M., Cividini, S., Marson, A. G. & Tudur Smith, C. Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data. Cochrane Database Syst. Rev. 4, CD011412 (2022).PubMed 

Google Scholar 
Kaplan, Y. C. & Demir, O. Use of phenytoin, phenobarbital carbamazepine, levetiracetam lamotrigine and valproate in pregnancy and breastfeeding: risk of major malformations, dose-dependency, monotherapy vs polytherapy. Pharmacokinetics Clin. Impl. Curr. Neuropharmacol. 19, 1805–1824 (2021).Article 
CAS 

Google Scholar 
Chen, Z., Brodie, M. J. & Kwan, P. What has been the impact of new drug treatments on epilepsy?. Curr. Opin. Neurol. 33, 185–190 (2020).Article 
PubMed 

Google Scholar 
Pinzi, L. & Rastelli, G. Molecular docking: Shifting paradigms in drug discovery. Int. J. Mol. Sci. 20, 4331 (2019).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Vemula, D., Jayasurya, P., Sushmitha, V., Kumar, Y. N. & Bhandari, V. CADD, AI and ML in drug discovery: A comprehensive review. Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 181, 106324 (2023).CAS 

Google Scholar 
Sivapalarajah, S. et al. The prescribable drugs with efficacy in experimental epilepsies (PDE3) database for drug repurposing research in epilepsy. Epilepsia 59, 492–501 (2018).Article 
PubMed 

Google Scholar 
Chen, M., Edwards, S. R. & Reutens, D. C. Complement in the development of post-traumatic epilepsy: Prospects for drug repurposing. J. Neurotrauma 37, 692–705 (2020).Article 
PubMed 

Google Scholar 
Brueggeman, L. et al. Drug repositioning in epilepsy reveals novel antiseizure candidates. Ann. Clin. Transl. Neurol. 6, 295–309 (2019).Article 
CAS 
PubMed 

Google Scholar 
Smith, C. M., Santalucia, M., Bunn, H. & Muzyk, A. Sublingual dexmedetomidine for the treatment of agitation in patients with schizophrenia and bipolar disorder. Clin. Psychopharmacol. Neurosci. Off. Sci. J. Korean Coll. Neuropsychopharmacol. 21, 215–221 (2023).Article 
CAS 

Google Scholar 
McGinn, R. J., Von Stein, E. L., Summers Stromberg, J. E. & Li, Y. Precision medicine in epilepsy. Prog. Mol. Biol. Transl. Sci. 190, 147–188 (2022).Article 
CAS 
PubMed 

Google Scholar 
Symonds, J. D., Zuberi, S. M. & Johnson, M. R. Advances in epilepsy gene discovery and implications for epilepsy diagnosis and treatment. Curr. Opin. Neurol. 30, 193–199 (2017).Article 
PubMed 

Google Scholar 
Meldrum, B. S. & Rogawski, M. A. Molecular targets for antiepileptic drug development. Neurother. J. Am. Soc. Exp. Neurother. 4, 18–61 (2007).CAS 

Google Scholar 
Guo, J., Liu, Q., Guo, H. & Lu, X. Ligandformer: A graph neural network for predicting compound property with robust interpretation. Preprint at http://arxiv.org/abs/2202.10873 (2022).Meng, F., Xi, Y., Huang, J. & Ayers, P. W. A curated diverse molecular database of blood-brain barrier permeability with chemical descriptors. Sci. Data 8, 289 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Goel, R. & Goel, A. Nebivolol enhances the anticonvulsant effect of gabapentin against various animal models of epilepsy in mice. J. Pharm. Res. 6, 364–367 (2013).CAS 

Google Scholar 
Dhamodharan, A., Selvaraj, N. & Meenakshi, R. Anticonvulsant effect of nebivolol alone and in combination with phenytoin against maximal electroshock-induced seizures in mice. J. Clin. Diagn. Res. https://doi.org/10.7860/JCDR/2021/47167.14669 (2021).Article 

Google Scholar 
Borowicz-Reutt, K. K., Banach, M. & Rudkowska, M. Nebivolol attenuates the anticonvulsant action of carbamazepine and phenobarbital against the maximal electroshock-induced seizures in mice. Pharmacol. Rep. PR 72, 80–86 (2020).Article 
CAS 
PubMed 

Google Scholar 
Hedges, D., Jeppson, K. & Whitehead, P. Antipsychotic medication and seizures: a review. Drugs Today Barc. Spain 1998(39), 551–557 (2003).Article 

Google Scholar 
Larkin, C. Epileptogenic effect of pimozide. Am. J. Psychiatry 140, 372–373 (1983).Article 
CAS 
PubMed 

Google Scholar 
He, S. et al. Drug repositioning for amyloid transthyretin amyloidosis by interactome network corrected by graph neural networks and transcriptome analysis. Hum. Gene Ther. 35, 70–79 (2024).Article 
CAS 
PubMed 

Google Scholar 
Kakiuchi, C. et al. Association analysis of HSP90B1 with bipolar disorder. J. Hum. Genet. 52, 794–803 (2007).Article 
CAS 
PubMed 

Google Scholar 
Gambardella, A. & Labate, A. The role of calcium channel mutations in human epilepsy. Prog. Brain Res. 213, 87–96 (2014).Article 
PubMed 

Google Scholar 
Le Roux, M. et al. CACNA1A-associated epilepsy: Electroclinical findings and treatment response on seizures in 18 patients. Eur. J. Paediatr. Neurol. EJPN Off J. Eur. Paediatr. Neurol. Soc. 33, 75–85 (2021).Article 

Google Scholar 
Sills, G. J. & Rogawski, M. A. Mechanisms of action of currently used antiseizure drugs. Neuropharmacology 168, 107966 (2020).Article 
CAS 
PubMed 

Google Scholar 
White, J. PubMed 2.0. Med. Ref. Serv. Q. 39, 382–387 (2020).Article 
PubMed 

Google Scholar 
Amberger, J. S. & Hamosh, A. Searching online mendelian inheritance in man (OMIM): A knowledgebase of human genes and genetic phenotypes. Curr. Protoc. Bioinforma. 58, 121–1212 (2017).Article 

Google Scholar 
Weaver, S. & Gleeson, M. P. The importance of the domain of applicability in QSAR modeling. J. Mol. Graph. Model. 26, 1315–1326 (2008).Article 
CAS 
PubMed 

Google Scholar 
Sahigara, F. et al. Comparison of different approaches to define the applicability domain of QSAR models. Molecules 17, 4791–4810 (2012).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Wu, Z. et al. MoleculeNet: a benchmark for molecular machine learning. Chem. Sci. 9, 513–530 (2018).Article 
CAS 
PubMed 

Google Scholar 
Berman, H. M. et al. The protein data bank. Nucleic Acids Res. 28, 235–242 (2000).Article 
ADS 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Wishart, D. S. et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 46, D1074–D1082 (2018).Article 
CAS 
PubMed 

Google Scholar 
Sastry, G. M., Adzhigirey, M., Day, T., Annabhimoju, R. & Sherman, W. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J. Comput. Aided Mol. Des. 27, 221–234 (2013).Article 
ADS 
PubMed 

Google Scholar 
Halgren, T. A. Identifying and characterizing binding sites and assessing druggability. J. Chem. Inf. Model. 49, 377–389 (2009).Article 
CAS 
PubMed 

Google Scholar 
Friesner, R. A. et al. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem. 47, 1739–1749 (2004).Article 
CAS 
PubMed 

Google Scholar 
Halgren, T. A. et al. Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J. Med. Chem. 47, 1750–1759 (2004).Article 
CAS 
PubMed 

Google Scholar 
Case, D. A. et al. AmberTools. J. Chem. Inf. Model. 63, 6183–6191 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Lomize, A. L., Pogozheva, I. D., Lomize, M. A. & Mosberg, H. I. Positioning of proteins in membranes: A computational approach. Protein Sci. 15, 1318–1333 (2006).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Jo, S., Kim, T., Iyer, V. G. & Im, W. CHARMM-GUI: a web-based graphical user interface for CHARMM. J. Comput. Chem. 29, 1859–1865 (2008).Article 
CAS 
PubMed 

Google Scholar 
Tian, C. et al. ff19SB: Amino-acid-specific protein backbone parameters trained against quantum mechanics energy surfaces in solution. J. Chem. Theory Comput. 16, 528–552 (2020).Article 
PubMed 

Google Scholar 
Dickson, C. J., Walker, R. C. & Gould, I. R. Lipid21: Complex lipid membrane simulations with AMBER. J. Chem. Theory Comput. 18, 1726–1736 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Ryckaert, J.-P., Ciccotti, G. & Berendsen, H. J. C. Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. J. Comput. Phys. 23, 327–341 (1977).Article 
ADS 
CAS 

Google Scholar 
Essmann, U. et al. A smooth particle mesh Ewald method. J. Chem. Phys. 103, 8577–8593 (1995).Article 
ADS 
CAS 

Google Scholar 
Pastor, R. W., Brooks, B. R. & Szabo, A. An analysis of the accuracy of Langevin and molecular dynamics algorithms. Mol. Phys. 65, 1409–1419 (1988).Article 
ADS 

Google Scholar 
Ashburner, M. et al. Gene Ontology: Tool for the unification of biology. Nat. Genet. 25, 25–29 (2000).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Aleksander, S. A. et al. The gene ontology knowledgebase in 2023. Genetics 224, iyad031 (2023).Article 
PubMed 
PubMed Central 

Google Scholar 
Huang, D. W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44–57 (2009).Article 
CAS 
PubMed 

Google Scholar 
Sherman, B. T. et al. DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 50, W216–W221 (2022).Article 
ADS 
CAS 
PubMed 
PubMed Central 

Google Scholar