# Improving generalisability of 3D binding affinity models in low data regimes

arXiv: https://arxiv.org/abs/2409.12995 · HTML: https://mlsanity.com/paper/2409.12995/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 7 of its 29 references that are in the map.
- First posted on arXiv 19 Sep 2024.

## Builds on (most cited first, 7 of 7)

- [XGBoost: A Scalable Tree Boosting System](https://mlsanity.com/paper/1603.02754/) (2016)
- [E(3)-Equivariant Graph Neural Networks for Data-Efficient and Accurate Interatomic Potentials](https://mlsanity.com/paper/2101.03164/) (2021)
- [Equivariant Diffusion for Molecule Generation in 3D](https://mlsanity.com/paper/2203.17003/) (2022)
- [MACE: Higher Order Equivariant Message Passing Neural Networks for Fast and Accurate Force Fields](https://mlsanity.com/paper/2206.07697/) (2022)
- [Learning Local Equivariant Representations for Large-Scale Atomistic Dynamics](https://mlsanity.com/paper/2204.05249/) (2022)
- [Structure-aware Interactive Graph Neural Networks for the Prediction of Protein-Ligand Binding Affinity](https://mlsanity.com/paper/2107.10670/) (2021)
- [SS-GNN: A Simple-Structured Graph Neural Network for Affinity Prediction](https://mlsanity.com/paper/2206.07015/) (2022)

## Abstract (arXiv)

Predicting protein-ligand binding affinity is an essential part of computer-aided drug design. However, generalisable and performant global binding affinity models remain elusive, particularly in low data regimes. Despite the evolution of model architectures, current benchmarks are not well-suited to probe the generalisability of 3D binding affinity models. Furthermore, 3D global architectures such as GNNs have not lived up to performance expectations. To investigate these issues, we introduce a novel split of the PDBBind dataset, minimizing similarity leakage between train and test sets and allowing for a fair and direct comparison between various model architectures. On this low similarity split, we demonstrate that, in general, 3D global models are superior to protein-specific local models in low data regimes. We also demonstrate that the performance of GNNs benefits from three novel contributions: supervised pre-training via quantum mechanical data, unsupervised pre-training via small molecule diffusion, and explicitly modeling hydrogen atoms in the input graph. We believe that this work introduces promising new approaches to unlock the potential of GNN architectures for binding affinity modelling.