# Secondary Structure-Guided Novel Protein Sequence Generation with Latent Graph Diffusion

arXiv: https://arxiv.org/abs/2407.07443 · HTML: https://mlsanity.com/paper/2407.07443/

## Key facts

- Cited by 5 papers in the map (data through 14 Oct 2026).
- Builds on 14 of its 51 references that are in the map.
- First posted on arXiv 10 Jul 2024.

## Builds on (most cited first, 14 of 14)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [Exploring the Limits of Transfer Learning with a Unified Text-to-Text Transformer](https://mlsanity.com/paper/1910.10683/) (2019)
- [RoFormer: Enhanced Transformer with Rotary Position Embedding](https://mlsanity.com/paper/2104.09864/) (2021)
- [Fast Graph Representation Learning with PyTorch Geometric](https://mlsanity.com/paper/1903.02428/) (2019)
- [Structured Denoising Diffusion Models in Discrete State-Spaces](https://mlsanity.com/paper/2107.03006/) (2021)
- [E(n) Equivariant Graph Neural Networks](https://mlsanity.com/paper/2102.09844/) (2021)
- [ProtTrans: Towards Cracking the Language of Life's Code Through Self-Supervised Deep Learning and High Performance Computing](https://mlsanity.com/paper/2007.06225/) (2020)
- [ProGen2: Exploring the Boundaries of Protein Language Models](https://mlsanity.com/paper/2206.13517/) (2022)
- [Graph Denoising Diffusion for Inverse Protein Folding](https://mlsanity.com/paper/2306.16819/) (2023)
- [Improved motif-scaffolding with SE(3) flow matching](https://mlsanity.com/paper/2401.04082/) (2024)
- [Str2Str: A Score-based Framework for Zero-shot Protein Conformation Sampling](https://mlsanity.com/paper/2306.03117/) (2023)
- [PoET: A generative model of protein families as sequences-of-sequences](https://mlsanity.com/paper/2306.06156/) (2023)

## Built on by (most cited first, 5 of 5)

- [Graph-based Unsupervised Disentangled Representation Learning via Multimodal Large Language Models](https://mlsanity.com/paper/2407.18999/) (2024)
- [PDFBench: A Benchmark for De novo Protein Design from Function](https://mlsanity.com/paper/2505.20346/) (2025)
- [Demystify Protein Generation with Hierarchical Conditional Diffusion Models](https://mlsanity.com/paper/2507.18603/) (2025)
- [BadGraph: A Backdoor Attack Against Latent Diffusion Model for Text-Guided Graph Generation](https://mlsanity.com/paper/2510.20792/) (2025)
- [Breaking the Bottlenecks: Scalable Diffusion Models for 3D Molecular Generation](https://mlsanity.com/paper/2601.08963/) (2026)

## Abstract (arXiv)

The advent of deep learning has introduced efficient approaches for de novo protein sequence design, significantly improving success rates and reducing development costs compared to computational or experimental methods. However, existing methods face challenges in generating proteins with diverse lengths and shapes while maintaining key structural features. To address these challenges, we introduce CPDiffusion-SS, a latent graph diffusion model that generates protein sequences based on coarse-grained secondary structural information. CPDiffusion-SS offers greater flexibility in producing a variety of novel amino acid sequences while preserving overall structural constraints, thus enhancing the reliability and diversity of generated proteins. Experimental analyses demonstrate the significant superiority of the proposed method in producing diverse and novel sequences, with CPDiffusion-SS surpassing popular baseline methods on open benchmarks across various quantitative measurements. Furthermore, we provide a series of case studies to highlight the biological significance of the generation performance by the proposed method. The source code is publicly available at https://github.com/riacd/CPDiffusion-SS