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      Optimization of Molecules via Deep Reinforcement Learning

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          Abstract

          We present a framework, which we call Molecule Deep Q-Networks (MolDQN), for molecule optimization by combining domain knowledge of chemistry and state-of-the-art reinforcement learning techniques (double Q-learning and randomized value functions). We directly define modifications on molecules, thereby ensuring 100% chemical validity. Further, we operate without pre-training on any dataset to avoid possible bias from the choice of that set. MolDQN achieves comparable or better performance against several other recently published algorithms for benchmark molecular optimization tasks. However, we also argue that many of these tasks are not representative of real optimization problems in drug discovery. Inspired by problems faced during medicinal chemistry lead optimization, we extend our model with multi-objective reinforcement learning, which maximizes drug-likeness while maintaining similarity to the original molecule. We further show the path through chemical space to achieve optimization for a molecule to understand how the model works.

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          The generalisation of student's problems when several different population variances are involved.

          B L WELCH (1947)
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            Molecular de-novo design through deep reinforcement learning

            This work introduces a method to tune a sequence-based generative model for molecular de novo design that through augmented episodic likelihood can learn to generate structures with certain specified desirable properties. We demonstrate how this model can execute a range of tasks such as generating analogues to a query structure and generating compounds predicted to be active against a biological target. As a proof of principle, the model is first trained to generate molecules that do not contain sulphur. As a second example, the model is trained to generate analogues to the drug Celecoxib, a technique that could be used for scaffold hopping or library expansion starting from a single molecule. Finally, when tuning the model towards generating compounds predicted to be active against the dopamine receptor type 2, the model generates structures of which more than 95% are predicted to be active, including experimentally confirmed actives that have not been included in either the generative model nor the activity prediction model. Graphical abstract . Electronic supplementary material The online version of this article (doi:10.1186/s13321-017-0235-x) contains supplementary material, which is available to authorized users.
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              A Markovian Decision Process

                Author and article information

                Contributors
                pfr@google.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                24 July 2019
                24 July 2019
                2019
                : 9
                : 10752
                Affiliations
                [1 ]ISNI 0000000419368956, GRID grid.168010.e, Department of Chemistry, , Stanford University, ; Stanford, California USA
                [2 ]GRID grid.420451.6, Google Research Applied Science, ; Mountain View, California USA
                [3 ]Work done during an internship at Google Research Applied Science, Mountain View, California USA
                Author information
                http://orcid.org/0000-0002-3282-9468
                http://orcid.org/0000-0003-4579-4388
                http://orcid.org/0000-0003-0797-0272
                Article
                47148
                10.1038/s41598-019-47148-x
                6656766
                31341196
                003411d3-bd4f-428b-b223-61d743813990
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 5 March 2019
                : 10 July 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000001, National Science Foundation (NSF);
                Award ID: CHE-1734082
                Award ID: CHE-1734082
                Award Recipient :
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                © The Author(s) 2019

                Uncategorized
                cheminformatics
                Uncategorized
                cheminformatics

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