# SculptDrug : A Spatial Condition-Aware Bayesian Flow Model for Structure-based Drug Design

arXiv: https://arxiv.org/abs/2511.12489 · HTML: https://mlsanity.com/paper/2511.12489/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 18 of its 52 references that are in the map.
- First posted on arXiv 16 Nov 2025.

## Builds on (most cited first, 18 of 18)

- [Generative Adversarial Networks](https://mlsanity.com/paper/2203.00667/) (2022)
- [Auto-Encoding Variational Bayes](https://mlsanity.com/paper/1312.6114/) (2013)
- [Junction Tree Variational Autoencoder for Molecular Graph Generation](https://mlsanity.com/paper/1802.04364/) (2018)
- [Constrained Graph Variational Autoencoders for Molecule Design](https://mlsanity.com/paper/1805.09076/) (2018)
- [Pocket2Mol: Efficient Molecular Sampling Based on 3D Protein Pockets](https://mlsanity.com/paper/2205.07249/) (2022)
- [A 3D Generative Model for Structure-Based Drug Design](https://mlsanity.com/paper/2203.10446/) (2022)
- [Generating 3D Molecules for Target Protein Binding](https://mlsanity.com/paper/2204.09410/) (2022)
- [Bayesian Flow Networks](https://mlsanity.com/paper/2308.07037/) (2023)
- [DiffBP: Generative Diffusion of 3D Molecules for Target Protein Binding](https://mlsanity.com/paper/2211.11214/) (2022)
- [MolCRAFT: Structure-Based Drug Design in Continuous Parameter Space](https://mlsanity.com/paper/2404.12141/) (2024)
- [Structure-based drug design with geometric deep learning](https://mlsanity.com/paper/2210.11250/) (2022)
- [Molecular Generation with Recurrent Neural Networks (RNNs)](https://mlsanity.com/paper/1705.04612/) (2017)
- [Generating 3D Molecular Structures Conditional on a Receptor Binding Site with Deep Generative Models](https://mlsanity.com/paper/2010.14442/) (2020)
- [Functional-Group-Based Diffusion for Pocket-Specific Molecule Generation and Elaboration](https://mlsanity.com/paper/2306.13769/) (2023)
- [Structure-based drug design by denoising voxel grids](https://mlsanity.com/paper/2405.03961/) (2024)
- [CBGBench: Fill in the Blank of Protein-Molecule Complex Binding Graph](https://mlsanity.com/paper/2406.10840/) (2024)
- [SurfPro: Functional Protein Design Based on Continuous Surface](https://mlsanity.com/paper/2405.06693/) (2024)
- [Exploring Hierarchical Molecular Graph Representation in Multimodal LLMs](https://mlsanity.com/paper/2411.04708/) (2024)

## Abstract (arXiv)

Structure-Based drug design (SBDD) has emerged as a popular approach in drug discovery, leveraging three-dimensional protein structures to generate drug ligands. However, existing generative models encounter several key challenges: (1) incorporating boundary condition constraints, (2) integrating hierarchical structural conditions, and (3) ensuring spatial modeling fidelity. To address these limitations, we propose SculptDrug, a spatial condition-aware generative model based on Bayesian flow networks (BFNs). First, SculptDrug follows a BFN-based framework and employs a progressive denoising strategy to ensure spatial modeling fidelity, iteratively refining atom positions while enhancing local interactions for precise spatial alignment. Second, we introduce a Boundary Awareness Block that incorporates protein surface constraints into the generative process to ensure that generated ligands are geometrically compatible with the target protein. Third, we design a Hierarchical Encoder that captures global structural context while preserving fine-grained molecular interactions, ensuring overall consistency and accurate ligand-protein conformations. We evaluate SculptDrug on the CrossDocked dataset, and experimental results demonstrate that SculptDrug outperforms state-of-the-art baselines, highlighting the effectiveness of spatial condition-aware modeling.