Balancing Exploration and Exploitation: Disentangled $β$-CVAE in De Novo Drug Design
This work addresses the problem of generating optimized drug-like molecules for pharmaceutical researchers, but it is incremental as it builds on existing CVAE methods with specific tuning.
The paper tackled the challenge of balancing exploration and exploitation in de novo drug design using a molecular-graph β-CVAE model, achieving results such as generating molecules with 41.07% ± 0.01% ClogP and 30.07% ± 0.01% for multivariate properties.
Deep generative models have recently emerged as a promising de novo drug design method. In this respect, deep generative conditional variational autoencoder (CVAE) models are a powerful approach for generating novel molecules with desired drug-like properties. However, molecular graph-based models with disentanglement and multivariate explicit latent conditioning have not been fully elucidated. To address this, we proposed a molecular-graph $β$-CVAE model for de novo drug design. Here, we empirically tuned the value of disentanglement and assessed its ability to generate molecules with optimised univariate- or-multivariate properties. In particular, we optimised the octanol-water partition coefficient (ClogP), molar refractivity (CMR), quantitative estimate of drug-likeness (QED), and synthetic accessibility score (SAS). Results suggest that a lower $β$ value increases the uniqueness of generated molecules (exploration). Univariate optimisation results showed our model generated molecular property averages of ClogP = 41.07% $\pm$ 0.01% and CMR 66.76% $\pm$ 0.01% by the Ghose filter. Multivariate property optimisation results showed that our model generated an average of 30.07% $\pm$ 0.01% molecules for both desired properties. Furthermore, our model improved the QED and SAS (exploitation) of molecules generated. Together, these results suggest that the $β$-CVAE could balance exploration and exploitation through disentanglement and is a promising model for de novo drug design, thus providing a basis for future studies.