Dataset Information

Generative Model for Proposing Drug Candidates Satisfying Anticancer Properties Using a Conditional Variational Autoencoder.

ABSTRACT: Deep learning-based molecular generative models have successfully identified drug candidates with desired properties against biological targets of interest. However, syntactically invalid molecules generated from a deep learning-generated model hinder the model from being applied to drug discovery. Herein, we propose a conditional variational autoencoder (CVAE) as a generative model to propose drug candidates with the desired property outside a data set range. We train the CVAE using molecular fingerprints and corresponding GI50 (inhibition of growth by 50%) results for breast cancer cell lines instead of training with various physical properties for each molecule together. We confirm that the generated fingerprints, not included in the training data set, represent the desired property using the CVAE model. In addition, our method can be used as a query expansion method for searching databases because fingerprints generated using our method can be regarded as expanded queries.

SUBMITTER: Joo S

PROVIDER: S-EPMC7407547 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Generative Model for Proposing Drug Candidates Satisfying Anticancer Properties Using a Conditional Variational Autoencoder.

Joo Sunghoon S Kim Min Soo MS Yang Jaeho J Park Jeahyun J

ACS omega 20200724 30

Deep learning-based molecular generative models have successfully identified drug candidates with desired properties against biological targets of interest. However, syntactically invalid molecules generated from a deep learning-generated model hinder the model from being applied to drug discovery. Herein, we propose a conditional variational autoencoder (CVAE) as a generative model to propose drug candidates with the desired property outside a data set range. We train the CVAE using molecular f ...[more]

PMID: 32775866

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Project description:Drug design is an important area of study for pharmaceutical businesses. However, low efficacy, off-target delivery, time consumption, and high cost are challenges and can create barriers that impact this process. Deep Learning models are emerging as a promising solution to perform de novo drug design, i.e., to generate drug-like molecules tailored to specific needs. However, stereochemistry was not explicitly considered in the generated molecules, which is inevitable in targeted-oriented molecules. This paper proposes a framework based on Feedback Generative Adversarial Network (GAN) that includes optimization strategy by incorporating Encoder-Decoder, GAN, and Predictor deep models interconnected with a feedback loop. The Encoder-Decoder converts the string notations of molecules into latent space vectors, effectively creating a new type of molecular representation. At the same time, the GAN can learn and replicate the training data distribution and, therefore, generate new compounds. The feedback loop is designed to incorporate and evaluate the generated molecules according to the multiobjective desired property at every epoch of training to ensure a steady shift of the generated distribution towards the space of the targeted properties. Moreover, to develop a more precise set of molecules, we also incorporate a multiobjective optimization selection technique based on a non-dominated sorting genetic algorithm. The results demonstrate that the proposed framework can generate realistic, novel molecules that span the chemical space. The proposed Encoder-Decoder model correctly reconstructs 99% of the datasets, including stereochemical information. The model's ability to find uncharted regions of the chemical space was successfully shown by optimizing the unbiased GAN to generate molecules with a high binding affinity to the Kappa Opioid and Adenosine [Formula: see text] receptor. Furthermore, the generated compounds exhibit high internal and external diversity levels 0.88 and 0.94, respectively, and uniqueness.

Dataset Information

Generative Model for Proposing Drug Candidates Satisfying Anticancer Properties Using a Conditional Variational Autoencoder.

Publications

Generative Model for Proposing Drug Candidates Satisfying Anticancer Properties Using a Conditional Variational Autoencoder.

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