# Objective-Agnostic Enhancement of Molecule Properties via Multi-Stage VAE

arXiv: https://arxiv.org/abs/2308.13066 · HTML: https://mlsanity.com/paper/2308.13066/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 26 of its 45 references that are in the map.
- First posted on arXiv 24 Aug 2023.

## Builds on (most cited first, 26 of 26)

- [Automatic chemical design using a data-driven continuous representation of molecules](https://mlsanity.com/paper/1610.02415/) (2016)
- [Convolutional Networks on Graphs for Learning Molecular Fingerprints](https://mlsanity.com/paper/1509.09292/) (2015)
- [Equivariant Diffusion for Molecule Generation in 3D](https://mlsanity.com/paper/2203.17003/) (2022)
- [Junction Tree Variational Autoencoder for Molecular Graph Generation](https://mlsanity.com/paper/1802.04364/) (2018)
- [DiGress: Discrete Denoising diffusion for graph generation](https://mlsanity.com/paper/2209.14734/) (2022)
- [GeoDiff: a Geometric Diffusion Model for Molecular Conformation Generation](https://mlsanity.com/paper/2203.02923/) (2022)
- [GraphVAE: Towards Generation of Small Graphs Using Variational Autoencoders](https://mlsanity.com/paper/1802.03480/) (2018)
- [Analyzing Learned Molecular Representations for Property Prediction](https://mlsanity.com/paper/1904.01561/) (2019)
- [Graph Convolutional Policy Network for Goal-Directed Molecular Graph Generation](https://mlsanity.com/paper/1806.02473/) (2018)
- [GuacaMol: Benchmarking Models for De Novo Molecular Design](https://mlsanity.com/paper/1811.09621/) (2018)
- [Grammar Variational Autoencoder](https://mlsanity.com/paper/1703.01925/) (2017)
- [Molecular Sets (MOSES): A Benchmarking Platform for Molecular Generation Models](https://mlsanity.com/paper/1811.12823/) (2018)
- [Hierarchical Generation of Molecular Graphs using Structural Motifs](https://mlsanity.com/paper/2002.03230/) (2020)
- [Fr'echet ChemNet Distance: A metric for generative models for molecules in drug discovery](https://mlsanity.com/paper/1803.09518/) (2018)
- [Diagnosing and Enhancing VAE Models](https://mlsanity.com/paper/1903.05789/) (2019)
- [Constrained Graph Variational Autoencoders for Molecule Design](https://mlsanity.com/paper/1805.09076/) (2018)
- [Symmetry-adapted generation of 3d point sets for the targeted discovery of molecules](https://mlsanity.com/paper/1906.00957/) (2019)
- [E(n) Equivariant Normalizing Flows](https://mlsanity.com/paper/2105.09016/) (2021)
- [A 3D Generative Model for Structure-Based Drug Design](https://mlsanity.com/paper/2203.10446/) (2022)
- [Objective-Reinforced Generative Adversarial Networks (ORGAN) for Sequence Generation Models](https://mlsanity.com/paper/1705.10843/) (2017)
- [Syntax-Directed Variational Autoencoder for Structured Data](https://mlsanity.com/paper/1802.08786/) (2018)
- [Inverse design of 3d molecular structures with conditional generative neural networks](https://mlsanity.com/paper/2109.04824/) (2021)
- [Learning to Extend Molecular Scaffolds with Structural Motifs](https://mlsanity.com/paper/2103.03864/) (2021)
- [Application of generative autoencoder in de novo molecular design](https://mlsanity.com/paper/1711.07839/) (2017)
- [Message-passing neural networks for high-throughput polymer screening](https://mlsanity.com/paper/1807.10363/) (2018)
- [Variational autoencoders in the presence of low-dimensional data: landscape and implicit bias](https://mlsanity.com/paper/2112.06868/) (2021)

## Abstract (arXiv)

Variational autoencoder (VAE) is a popular method for drug discovery and various architectures and pipelines have been proposed to improve its performance. However, VAE approaches are known to suffer from poor manifold recovery when the data lie on a low-dimensional manifold embedded in a higher dimensional ambient space [Dai and Wipf, 2019]. The consequences of it in drug discovery are somewhat under-explored. In this paper, we explore applying a multi-stage VAE approach, that can improve manifold recovery on a synthetic dataset, to the field of drug discovery. We experimentally evaluate our multi-stage VAE approach using the ChEMBL dataset and demonstrate its ability to improve the property statistics of generated molecules substantially from pre-existing methods without incorporating property predictors into the training pipeline. We further fine-tune our models on two curated and much smaller molecule datasets that target different proteins. Our experiments show an increase in the number of active molecules generated by the multi-stage VAE in comparison to their one-stage equivalent. For each of the two tasks, our baselines include methods that use learned property predictors to incorporate target metrics directly into the training objective and we discuss complications that arise with this methodology.