# ProtPainter: Draw or Drag Protein via Topology-guided Diffusion

arXiv: https://arxiv.org/abs/2504.14274 · HTML: https://mlsanity.com/paper/2504.14274/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Placed in Flow matching, time series and science, one of 14 directions in Diffusion models.
- Builds on 14 of its 49 references that are in the map.
- First posted on arXiv 19 Apr 2025.

## 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, 14 of 14)

- [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)
- [Deep Unsupervised Learning using Nonequilibrium Thermodynamics](https://mlsanity.com/paper/1503.03585/) (2015)
- [E(n) Equivariant Graph Neural Networks](https://mlsanity.com/paper/2102.09844/) (2021)
- [ILVR: Conditioning Method for Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2108.02938/) (2021)
- [Analog Bits: Generating Discrete Data using Diffusion Models with Self-Conditioning](https://mlsanity.com/paper/2208.04202/) (2022)
- [SE(3) diffusion model with application to protein backbone generation](https://mlsanity.com/paper/2302.02277/) (2023)
- [SE(3)-Stochastic Flow Matching for Protein Backbone Generation](https://mlsanity.com/paper/2310.02391/) (2023)
- [Geometrically Equivariant Graph Neural Networks: A Survey](https://mlsanity.com/paper/2202.07230/) (2022)
- [Generating Novel, Designable, and Diverse Protein Structures by Equivariantly Diffusing Oriented Residue Clouds](https://mlsanity.com/paper/2301.12485/) (2023)
- [Protein Conformation Generation via Force-Guided SE(3) Diffusion Models](https://mlsanity.com/paper/2403.14088/) (2024)
- [Out of Many, One: Designing and Scaffolding Proteins at the Scale of the Structural Universe with Genie 2](https://mlsanity.com/paper/2405.15489/) (2024)
- [Zero-Shot 3D Drug Design by Sketching and Generating](https://mlsanity.com/paper/2209.13865/) (2022)
- [Improving Antibody Design with Force-Guided Sampling in Diffusion Models](https://mlsanity.com/paper/2406.05832/) (2024)

## Built on by (most cited first, 1 of 1)

- [OS-SPEAR: A Toolkit for the Safety, Performance,Efficiency, and Robustness Analysis of OS Agents](https://mlsanity.com/paper/2604.24348/) (2026)

## Abstract (arXiv)

Recent advances in protein backbone generation have achieved promising results under structural, functional, or physical constraints. However, existing methods lack the flexibility for precise topology control, limiting navigation of the backbone space. We present ProtPainter, a diffusion-based approach for generating protein backbones conditioned on 3D curves. ProtPainter follows a two-stage process: curve-based sketching and sketch-guided backbone generation. For the first stage, we propose CurveEncoder, which predicts secondary structure annotations from a curve to parametrize sketch generation. For the second stage, the sketch guides the generative process in Denoising Diffusion Probabilistic Modeling (DDPM) to generate backbones. During this process, we further introduce a fusion scheduling scheme, Helix-Gating, to control the scaling factors. To evaluate, we propose the first benchmark for topology-conditioned protein generation, introducing Protein Restoration Task and a new metric, self-consistency Topology Fitness (scTF). Experiments demonstrate ProtPainter's ability to generate topology-fit (scTF > 0.8) and designable (scTM > 0.5) backbones, with drawing and dragging tasks showcasing its flexibility and versatility.