# Conditional β-VAE for De Novo Molecular Generation

arXiv: https://arxiv.org/abs/2205.01592 · HTML: https://mlsanity.com/paper/2205.01592/

## Key facts

- Cited by 8 papers in the map (data through 14 Oct 2026).
- Builds on 38 of its 57 references that are in the map.
- First posted on arXiv 1 May 2022.

## Builds on (most cited first, 30 of 38)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Auto-Encoding Variational Bayes](https://mlsanity.com/paper/1312.6114/) (2013)
- [On the Properties of Neural Machine Translation: Encoder-Decoder Approaches](https://mlsanity.com/paper/1409.1259/) (2014)
- [Automatic chemical design using a data-driven continuous representation of molecules](https://mlsanity.com/paper/1610.02415/) (2016)
- [TensorFlow: Large-Scale Machine Learning on Heterogeneous Distributed Systems](https://mlsanity.com/paper/1603.04467/) (2016)
- [Junction Tree Variational Autoencoder for Molecular Graph Generation](https://mlsanity.com/paper/1802.04364/) (2018)
- [Generating Sentences from a Continuous Space](https://mlsanity.com/paper/1511.06349/) (2015)
- [Unsupervised Image-to-Image Translation Networks](https://mlsanity.com/paper/1703.00848/) (2017)
- [GraphVAE: Towards Generation of Small Graphs Using Variational Autoencoders](https://mlsanity.com/paper/1802.03480/) (2018)
- [Graph Convolutional Policy Network for Goal-Directed Molecular Graph Generation](https://mlsanity.com/paper/1806.02473/) (2018)
- [GraphAF: a Flow-based Autoregressive Model for Molecular Graph Generation](https://mlsanity.com/paper/2001.09382/) (2020)
- [GuacaMol: Benchmarking Models for De Novo Molecular Design](https://mlsanity.com/paper/1811.09621/) (2018)
- [Optimization of Molecules via Deep Reinforcement Learning](https://mlsanity.com/paper/1810.08678/) (2018)
- [MoFlow: An Invertible Flow Model for Generating Molecular Graphs](https://mlsanity.com/paper/2006.10137/) (2020)
- [Long Short-Term Memory-Networks for Machine Reading](https://mlsanity.com/paper/1601.06733/) (2016)
- [Lagging Inference Networks and Posterior Collapse in Variational Autoencoders](https://mlsanity.com/paper/1901.05534/) (2019)
- [Sample-Efficient Optimization in the Latent Space of Deep Generative Models via Weighted Retraining](https://mlsanity.com/paper/2006.09191/) (2020)
- [Objective-Reinforced Generative Adversarial Networks (ORGAN) for Sequence Generation Models](https://mlsanity.com/paper/1705.10843/) (2017)
- [GraphNVP: An Invertible Flow Model for Generating Molecular Graphs](https://mlsanity.com/paper/1905.11600/) (2019)
- [Syntax-Directed Variational Autoencoder for Structured Data](https://mlsanity.com/paper/1802.08786/) (2018)
- [MolecularRNN: Generating realistic molecular graphs with optimized properties](https://mlsanity.com/paper/1905.13372/) (2019)
- [Molecular generative model based on conditional variational autoencoder for de novo molecular design](https://mlsanity.com/paper/1806.05805/) (2018)
- [Mol-CycleGAN - a generative model for molecular optimization](https://mlsanity.com/paper/1902.02119/) (2019)
- [Learning To Navigate The Synthetically Accessible Chemical Space Using Reinforcement Learning](https://mlsanity.com/paper/2004.12485/) (2020)
- [Molecular Hypergraph Grammar with its Application to Molecular Optimization](https://mlsanity.com/paper/1809.02745/) (2018)
- [High-Dimensional Bayesian Optimisation with Variational Autoencoders and Deep Metric Learning](https://mlsanity.com/paper/2106.03609/) (2021)
- [Conditional molecular design with deep generative models](https://mlsanity.com/paper/1805.00108/) (2018)
- [Message-passing neural networks for high-throughput polymer screening](https://mlsanity.com/paper/1807.10363/) (2018)
- [Variational AutoEncoder For Regression: Application to Brain Aging Analysis](https://mlsanity.com/paper/1904.05948/) (2019)

## Built on by (most cited first, 8 of 8)

- [Graph Neural Networks for Molecules](https://mlsanity.com/paper/2209.05582/) (2022)
- [LLamol: A Dynamic Multi-Conditional Generative Transformer for De Novo Molecular Design](https://mlsanity.com/paper/2311.14407/) (2023)
- [Faster and more diverse de novo molecular optimization with double-loop reinforcement learning using augmented SMILES](https://mlsanity.com/paper/2210.12458/) (2022)
- [Target Specific De Novo Design of Drug Candidate Molecules with Graph Transformer-based Generative Adversarial Networks](https://mlsanity.com/paper/2302.07868/) (2023)
- [Denoising Multi-Beta VAE: Representation Learning for Disentanglement and Generation](https://mlsanity.com/paper/2507.06613/) (2025)
- [Kernel-Elastic Autoencoder for Molecular Design](https://mlsanity.com/paper/2310.08685/) (2023)
- [Balancing Exploration and Exploitation: Disentangled β-CVAE in De Novo Drug Design](https://mlsanity.com/paper/2306.01683/) (2023)
- [HyperDiffusionFields (HyDiF): Diffusion-Guided Hypernetworks for Learning Implicit Molecular Neural Fields](https://mlsanity.com/paper/2510.18122/) (2025)

## Abstract (arXiv)

Deep learning has significantly advanced and accelerated de novo molecular generation. Generative networks, namely Variational Autoencoders (VAEs) can not only randomly generate new molecules, but also alter molecular structures to optimize specific chemical properties which are pivotal for drug-discovery. While VAEs have been proposed and researched in the past for pharmaceutical applications, they possess deficiencies which limit their ability to both optimize properties and decode syntactically valid molecules. We present a recurrent, conditional β-VAE which disentangles the latent space to enhance post hoc molecule optimization. We create a mutual information driven training protocol and data augmentations to both increase molecular validity and promote longer sequence generation. We demonstrate the efficacy of our framework on the ZINC-250k dataset, achieving SOTA unconstrained optimization results on the penalized LogP (pLogP) and QED scores, while also matching current SOTA results for validity, novelty and uniqueness scores for random generation. We match the current SOTA on QED for top-3 molecules at 0.948, while setting a new SOTA for pLogP optimization at 104.29, 90.12, 69.68 and demonstrating improved results on the constrained optimization task.