# Leveraging Side Information for Ligand Conformation Generation using Diffusion-Based Approaches

arXiv: https://arxiv.org/abs/2309.16684 · HTML: https://mlsanity.com/paper/2309.16684/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Flow matching, time series and science, one of 14 directions in Diffusion models.
- Builds on 23 of its 41 references that are in the map.
- First posted on arXiv 2 Aug 2023.

## Placed in

- Diffusion models / [Flow matching, time series and science](https://mlsanity.com/diffusion/flow-matching-time-series-and-science/)

## Builds on (most cited first, 23 of 23)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [Score-Based Generative Modeling through Stochastic Differential Equations](https://mlsanity.com/paper/2011.13456/) (2020)
- [DeepSDF: Learning Continuous Signed Distance Functions for Shape Representation](https://mlsanity.com/paper/1901.05103/) (2019)
- [Diffusion Models: A Comprehensive Survey of Methods and Applications](https://mlsanity.com/paper/2209.00796/) (2022)
- [E(n) Equivariant Graph Neural Networks](https://mlsanity.com/paper/2102.09844/) (2021)
- [Equivariant Diffusion for Molecule Generation in 3D](https://mlsanity.com/paper/2203.17003/) (2022)
- [SchNet: A continuous-filter convolutional neural network for modeling quantum interactions](https://mlsanity.com/paper/1706.08566/) (2017)
- [GeoDiff: a Geometric Diffusion Model for Molecular Conformation Generation](https://mlsanity.com/paper/2203.02923/) (2022)
- [DiffDock: Diffusion Steps, Twists, and Turns for Molecular Docking](https://mlsanity.com/paper/2210.01776/) (2022)
- [GraphAF: a Flow-based Autoregressive Model for Molecular Graph Generation](https://mlsanity.com/paper/2001.09382/) (2020)
- [Equivariant Flows: Exact Likelihood Generative Learning for Symmetric Densities](https://mlsanity.com/paper/2006.02425/) (2020)
- [GEOM: Energy-annotated molecular conformations for property prediction and molecular generation](https://mlsanity.com/paper/2006.05531/) (2020)
- [Geometric Latent Diffusion Models for 3D Molecule Generation](https://mlsanity.com/paper/2305.01140/) (2023)
- [EGSDE: Unpaired Image-to-Image Translation via Energy-Guided Stochastic Differential Equations](https://mlsanity.com/paper/2207.06635/) (2022)
- [Learning Gradient Fields for Molecular Conformation Generation](https://mlsanity.com/paper/2105.03902/) (2021)
- [EquiBind: Geometric Deep Learning for Drug Binding Structure Prediction](https://mlsanity.com/paper/2202.05146/) (2022)
- [Molecular geometry prediction using a deep generative graph neural network](https://mlsanity.com/paper/1904.00314/) (2019)
- [Learning Neural Generative Dynamics for Molecular Conformation Generation](https://mlsanity.com/paper/2102.10240/) (2021)
- [A Generative Model for Molecular Distance Geometry](https://mlsanity.com/paper/1909.11459/) (2019)
- [Equivariant Energy-Guided SDE for Inverse Molecular Design](https://mlsanity.com/paper/2209.15408/) (2022)
- [MolGenSurvey: A Systematic Survey in Machine Learning Models for Molecule Design](https://mlsanity.com/paper/2203.14500/) (2022)
- [Meta-PU: An Arbitrary-Scale Upsampling Network for Point Cloud](https://mlsanity.com/paper/2102.04317/) (2021)

## Abstract (arXiv)

Ligand molecule conformation generation is a critical challenge in drug discovery. Deep learning models have been developed to tackle this problem, particularly through the use of generative models in recent years. However, these models often generate conformations that lack meaningful structure and randomness due to the absence of essential side information. Examples of such side information include the chemical and geometric features of the target protein, ligand-target compound interactions, and ligand chemical properties. Without these constraints, the generated conformations may not be suitable for further selection and design of new drugs. To address this limitation, we propose a novel method for generating ligand conformations that leverage side information and incorporate flexible constraints into standard diffusion models. Drawing inspiration from the concept of message passing, we introduce ligand-target massage passing block, a mechanism that facilitates the exchange of information between target nodes and ligand nodes, thereby incorporating target node features. To capture non-covalent interactions, we introduce ligand-target compound inter and intra edges. To further improve the biological relevance of the generated conformations, we train energy models using scalar chemical features. These models guide the progress of the standard Denoising Diffusion Probabilistic Models, resulting in more biologically meaningful conformations. We evaluate the performance of SIDEGEN using the PDBBind-2020 dataset, comparing it against other methods. The results demonstrate improvements in both Aligned RMSD and Ligand RMSD evaluations. Specifically, our model outperforms GeoDiff (trained on PDBBind-2020) by 20% in terms of the median aligned RMSD metric.