# Target-aware Molecular Graph Generation

arXiv: https://arxiv.org/abs/2202.04829 · HTML: https://mlsanity.com/paper/2202.04829/

## Key facts

- Cited by 18 papers in the map (data through 14 Oct 2026).
- Builds on 37 of its 81 references that are in the map.
- First posted on arXiv 10 Feb 2022.

## Builds on (most cited first, 30 of 37)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Sequence to Sequence Learning with Neural Networks](https://mlsanity.com/paper/1409.3215/) (2014)
- [Density estimation using Real NVP](https://mlsanity.com/paper/1605.08803/) (2016)
- [Glow: Generative Flow with Invertible 1x1 Convolutions](https://mlsanity.com/paper/1807.03039/) (2018)
- [Understanding Contrastive Representation Learning through Alignment and Uniformity on the Hypersphere](https://mlsanity.com/paper/2005.10242/) (2020)
- [NICE: Non-linear Independent Components Estimation](https://mlsanity.com/paper/1410.8516/) (2014)
- [Pixel Recurrent Neural Networks](https://mlsanity.com/paper/1601.06759/) (2016)
- [Automatic chemical design using a data-driven continuous representation of molecules](https://mlsanity.com/paper/1610.02415/) (2016)
- [Junction Tree Variational Autoencoder for Molecular Graph Generation](https://mlsanity.com/paper/1802.04364/) (2018)
- [MolGAN: An implicit generative model for small molecular graphs](https://mlsanity.com/paper/1805.11973/) (2018)
- [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)
- [Grammar Variational Autoencoder](https://mlsanity.com/paper/1703.01925/) (2017)
- [Hierarchical Generation of Molecular Graphs using Structural Motifs](https://mlsanity.com/paper/2002.03230/) (2020)
- [MoFlow: An Invertible Flow Model for Generating Molecular Graphs](https://mlsanity.com/paper/2006.10137/) (2020)
- [GraphDF: A Discrete Flow Model for Molecular Graph Generation](https://mlsanity.com/paper/2102.01189/) (2021)
- [DeepDTA: Deep Drug-Target Binding Affinity Prediction](https://mlsanity.com/paper/1801.10193/) (2018)
- [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)
- [Noise Flow: Noise Modeling with Conditional Normalizing Flows](https://mlsanity.com/paper/1908.08453/) (2019)
- [Graph Normalizing Flows](https://mlsanity.com/paper/1905.13177/) (2019)
- [MolecularRNN: Generating realistic molecular graphs with optimized properties](https://mlsanity.com/paper/1905.13372/) (2019)
- [Learning towards Minimum Hyperspherical Energy](https://mlsanity.com/paper/1805.09298/) (2018)
- [VideoFlow: A Conditional Flow-Based Model for Stochastic Video Generation](https://mlsanity.com/paper/1903.01434/) (2019)
- [Molecular generative model based on conditional variational autoencoder for de novo molecular design](https://mlsanity.com/paper/1806.05805/) (2018)
- [Hierarchical Conditional Flow: A Unified Framework for Image Super-Resolution and Image Rescaling](https://mlsanity.com/paper/2108.05301/) (2021)
- [Mol-CycleGAN - a generative model for molecular optimization](https://mlsanity.com/paper/1902.02119/) (2019)
- [DeepAffinity: Interpretable Deep Learning of Compound-Protein Affinity through Unified Recurrent and Convolutional Neural Networks](https://mlsanity.com/paper/1806.07537/) (2018)
- [Learning Latent Subspaces in Variational Autoencoders](https://mlsanity.com/paper/1812.06190/) (2018)

## Built on by (most cited first, 18 of 18)

- [3D Equivariant Diffusion for Target-Aware Molecule Generation and Affinity Prediction](https://mlsanity.com/paper/2303.03543/) (2023)
- [Temporal Attention Unit: Towards Efficient Spatiotemporal Predictive Learning](https://mlsanity.com/paper/2206.12126/) (2022)
- [PiFold: Toward effective and efficient protein inverse folding](https://mlsanity.com/paper/2209.12643/) (2022)
- [A Comprehensive Survey on Deep Graph Representation Learning](https://mlsanity.com/paper/2304.05055/) (2023)
- [DiffBP: Generative Diffusion of 3D Molecules for Target Protein Binding](https://mlsanity.com/paper/2211.11214/) (2022)
- [Functional-Group-Based Diffusion for Pocket-Specific Molecule Generation and Elaboration](https://mlsanity.com/paper/2306.13769/) (2023)
- [Knowledge-Design: Pushing the Limit of Protein Design via Knowledge Refinement](https://mlsanity.com/paper/2305.15151/) (2023)
- [Enhancing Human-like Multi-Modal Reasoning: A New Challenging Dataset and Comprehensive Framework](https://mlsanity.com/paper/2307.12626/) (2023)
- [A Graph is Worth K Words: Euclideanizing Graph using Pure Transformer](https://mlsanity.com/paper/2402.02464/) (2024)
- [Cross-Gate MLP with Protein Complex Invariant Embedding is A One-Shot Antibody Designer](https://mlsanity.com/paper/2305.09480/) (2023)
- [Lost-in-Distance: Impact of Contextual Proximity on LLM Performance in Graph Tasks](https://mlsanity.com/paper/2410.01985/) (2024)
- [PrefixMol: Target- and Chemistry-aware Molecule Design via Prefix Embedding](https://mlsanity.com/paper/2302.07120/) (2023)
- [Prior-Guided Flow Matching for Target-Aware Molecule Design with Learnable Atom Number](https://mlsanity.com/paper/2509.01486/) (2025)
- [Efficiently Predicting Protein Stability Changes Upon Single-point Mutation with Large Language Models](https://mlsanity.com/paper/2312.04019/) (2023)
- [Manifold-Constrained Nucleus-Level Denoising Diffusion Model for Structure-Based Drug Design](https://mlsanity.com/paper/2409.10584/) (2024)
- [A 3D pocket-aware and affinity-guided diffusion model for lead optimization](https://mlsanity.com/paper/2504.21065/) (2025)
- [TextOmics-Guided Diffusion for Hit-like Molecular Generation](https://mlsanity.com/paper/2507.09982/) (2025)
- [Fine-Tuning Diffusion Models for Molecular Generation via Reinforcement Learning and Fast Sampling](https://mlsanity.com/paper/2606.01220/) (2026)

## Abstract (arXiv)

Generating molecules with desired biological activities has attracted growing attention in drug discovery. Previous molecular generation models are designed as chemocentric methods that hardly consider the drug-target interaction, limiting their practical applications. In this paper, we aim to generate molecular drugs in a target-aware manner that bridges biological activity and molecular design. To solve this problem, we compile a benchmark dataset from several publicly available datasets and build baselines in a unified framework. Building on the recent advantages of flow-based molecular generation models, we propose SiamFlow, which forces the flow to fit the distribution of target sequence embeddings in latent space. Specifically, we employ an alignment loss and a uniform loss to bring target sequence embeddings and drug graph embeddings into agreements while avoiding collapse. Furthermore, we formulate the alignment into a one-to-many problem by learning spaces of target sequence embeddings. Experiments quantitatively show that our proposed method learns meaningful representations in the latent space toward the target-aware molecular graph generation and provides an alternative approach to bridge biology and chemistry in drug discovery.