Direct steering of de novo molecular generation with descriptor conditional recurrent neural networks

• DOI: 10.1038/s42256-020-0174-5
• Publication Date: 2020-05-18T16:06:36Z
• Authors: Panagiotis-Christ...; Josep Arús-Pous; Hongming Chen; Ola Engkvist; Christian Tyrchan; Esben Jannik Bjerrum
• Keywords: 0303 health sciences; 03 medical and health sciences

Deep learning has acquired considerable momentum over the past couple of years in the domain of de novo drug design. Here, we propose a simple approach to the task of focused molecular generation for drug design purposes by constructing a conditional recurrent neural network (cRNN). We aggregate selected molecular descriptors and transform them into the initial memory state of the network before starting the generation of alphanumeric strings that describe molecules. We thus tackle the inverse design problem directly, as the cRNNs may generate molecules near the specified conditions. Moreover, we exemplify a novel way of assessing the focus of the conditional output of such a model using negative log-likelihood plots. The output is more focused than traditional unbiased RNNs, yet less focused than autoencoders, thus representing a novel method with intermediate output specificity between well-established methods. Conceptually, our architecture shows promise for the generalized problem of steering of sequential data generation with recurrent neural networks. The rise of deep neural networks allows for new ways to design molecules that interact with biological structures. An approach that uses conditional recurrent neural networks generates molecules with properties near specified conditions.