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DruganalogsLSTM-REV.pdf (1.56 MB)

Drug Analogs from Fragment Based Long Short-Term Memory Generative Neural Networks

revised on 22.02.2019, 10:19 and posted on 22.02.2019, 16:29 by Mahendra Awale, Finton Sirockin, Nikolaus Stiefl, Jean-Louis Reymond

Several recent reports have shown that long short-term memory generative neural networks (LSTM) of the type used for grammar learning efficiently learn to write SMILES of drug-like compounds when trained with SMILES from a database of bioactive compounds such as ChEMBL and can later produce focused sets upon transfer learning with compounds of specific bioactivity profiles. Here we trained an LSTM using molecules taken either from ChEMBL, DrugBank, commercially available fragments, or from FDB-17 (a database of fragments up to 17 atoms) and performed transfer learning to a single known drug to obtain new analogs of this drug. We found that this approach readily generates hundreds of relevant and diverse new drug analogs and works best with training sets of around 40,000 compounds as simple as commercial fragments. These data suggest that fragment-based LSTM offer a promising method for new molecule generation.


Email Address of Submitting Author


University of Bern, Novartis Institutes for Biomedical Research



ORCID For Submitting Author


Declaration of Conflict of Interest