# Ligandformer: A Graph Neural Network for Predicting Compound Property with Robust Interpretation

arXiv: https://arxiv.org/abs/2202.10873 · HTML: https://mlsanity.com/paper/2202.10873/

## Key facts

- Cited by 3 papers in the map (data through 14 Oct 2026).
- Builds on 19 of its 40 references that are in the map.
- First posted on arXiv 21 Feb 2022.

## Builds on (most cited first, 19 of 19)

- [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)
- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [Exploring the Limits of Transfer Learning with a Unified Text-to-Text Transformer](https://mlsanity.com/paper/1910.10683/) (2019)
- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [Graph Attention Networks](https://mlsanity.com/paper/1710.10903/) (2017)
- [End-to-End Object Detection with Transformers](https://mlsanity.com/paper/2005.12872/) (2020)
- [Inductive Representation Learning on Large Graphs](https://mlsanity.com/paper/1706.02216/) (2017)
- [Layer Normalization](https://mlsanity.com/paper/1607.06450/) (2016)
- [How Powerful are Graph Neural Networks?](https://mlsanity.com/paper/1810.00826/) (2018)
- [MoleculeNet: A Benchmark for Molecular Machine Learning](https://mlsanity.com/paper/1703.00564/) (2017)
- [Weisfeiler and Leman Go Neural: Higher-order Graph Neural Networks](https://mlsanity.com/paper/1810.02244/) (2018)
- [Efficient Transformers: A Survey](https://mlsanity.com/paper/2009.06732/) (2020)
- [Image Transformer](https://mlsanity.com/paper/1802.05751/) (2018)
- [Analyzing Learned Molecular Representations for Property Prediction](https://mlsanity.com/paper/1904.01561/) (2019)
- [AdaBelief Optimizer: Adapting Stepsizes by the Belief in Observed Gradients](https://mlsanity.com/paper/2010.07468/) (2020)
- [ASAP: Adaptive Structure Aware Pooling for Learning Hierarchical Graph Representations](https://mlsanity.com/paper/1911.07979/) (2019)
- [Chemi-net: a graph convolutional network for accurate drug property prediction](https://mlsanity.com/paper/1803.06236/) (2018)
- [Step Change Improvement in ADMET Prediction with PotentialNet Deep Featurization](https://mlsanity.com/paper/1903.11789/) (2019)

## Built on by (most cited first, 3 of 3)

- [Do Larger Models Really Win in Drug Discovery? A Benchmark Assessment of Model Scaling in AI-Driven Molecular Property and Activity Prediction](https://mlsanity.com/paper/2604.26498/) (2026)
- [GeoScatt-GNN: A Geometric Scattering Transform-Based Graph Neural Network Model for Ames Mutagenicity Prediction](https://mlsanity.com/paper/2411.15331/) (2024)
- [MolLedger: An Additive Graph Neural Network with Chemically Grounded ADME Attributions](https://mlsanity.com/paper/2608.30636/) (2026)

## Abstract (arXiv)

Robust and efficient interpretation of QSAR methods is quite useful to validate AI prediction rationales with subjective opinion (chemist or biologist expertise), understand sophisticated chemical or biological process mechanisms, and provide heuristic ideas for structure optimization in pharmaceutical industry. For this purpose, we construct a multi-layer self-attention based Graph Neural Network framework, namely Ligandformer, for predicting compound property with interpretation. Ligandformer integrates attention maps on compound structure from different network blocks. The integrated attention map reflects the machine's local interest on compound structure, and indicates the relationship between predicted compound property and its structure. This work mainly contributes to three aspects: 1. Ligandformer directly opens the black-box of deep learning methods, providing local prediction rationales on chemical structures. 2. Ligandformer gives robust prediction in different experimental rounds, overcoming the ubiquitous prediction instability of deep learning methods. 3. Ligandformer can be generalized to predict different chemical or biological properties with high performance. Furthermore, Ligandformer can simultaneously output specific property score and visible attention map on structure, which can support researchers to investigate chemical or biological property and optimize structure efficiently. Our framework outperforms over counterparts in terms of accuracy, robustness and generalization, and can be applied in complex system study.