Structure Language Models for Protein Conformation Generation
Fuente:
arXiv
Guardado en:
| Autores principales: | , , , , , , |
|---|---|
| Formato: | Preprint |
| Publicado: |
2024
|
| Materias: | |
| Acceso en línea: | |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| _version_ | 1866916651189927936 |
|---|---|
| author | Lu, Jiarui Chen, Xiaoyin Lu, Stephen Zhewen Shi, Chence Guo, Hongyu Bengio, Yoshua Tang, Jian |
| author_facet | Lu, Jiarui Chen, Xiaoyin Lu, Stephen Zhewen Shi, Chence Guo, Hongyu Bengio, Yoshua Tang, Jian |
| contents | Proteins adopt multiple structural conformations to perform their diverse biological functions, and understanding these conformations is crucial for advancing drug discovery. Traditional physics-based simulation methods often struggle with sampling equilibrium conformations and are computationally expensive. Recently, deep generative models have shown promise in generating protein conformations as a more efficient alternative. However, these methods predominantly rely on the diffusion process within a 3D geometric space, which typically centers around the vicinity of metastable states and is often inefficient in terms of runtime. In this paper, we introduce Structure Language Modeling (SLM) as a novel framework for efficient protein conformation generation. Specifically, the protein structures are first encoded into a compact latent space using a discrete variational auto-encoder, followed by conditional language modeling that effectively captures sequence-specific conformation distributions. This enables a more efficient and interpretable exploration of diverse ensemble modes compared to existing methods. Based on this general framework, we instantiate SLM with various popular LM architectures as well as proposing the ESMDiff, a novel BERT-like structure language model fine-tuned from ESM3 with masked diffusion. We verify our approach in various scenarios, including the equilibrium dynamics of BPTI, conformational change pairs, and intrinsically disordered proteins. SLM provides a highly efficient solution, offering a 20-100x speedup than existing methods in generating diverse conformations, shedding light on promising avenues for future research. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2410_18403 |
| institution | arXiv |
| publishDate | 2024 |
| record_format | arxiv |
| spellingShingle | Structure Language Models for Protein Conformation Generation Lu, Jiarui Chen, Xiaoyin Lu, Stephen Zhewen Shi, Chence Guo, Hongyu Bengio, Yoshua Tang, Jian Biomolecules Machine Learning Proteins adopt multiple structural conformations to perform their diverse biological functions, and understanding these conformations is crucial for advancing drug discovery. Traditional physics-based simulation methods often struggle with sampling equilibrium conformations and are computationally expensive. Recently, deep generative models have shown promise in generating protein conformations as a more efficient alternative. However, these methods predominantly rely on the diffusion process within a 3D geometric space, which typically centers around the vicinity of metastable states and is often inefficient in terms of runtime. In this paper, we introduce Structure Language Modeling (SLM) as a novel framework for efficient protein conformation generation. Specifically, the protein structures are first encoded into a compact latent space using a discrete variational auto-encoder, followed by conditional language modeling that effectively captures sequence-specific conformation distributions. This enables a more efficient and interpretable exploration of diverse ensemble modes compared to existing methods. Based on this general framework, we instantiate SLM with various popular LM architectures as well as proposing the ESMDiff, a novel BERT-like structure language model fine-tuned from ESM3 with masked diffusion. We verify our approach in various scenarios, including the equilibrium dynamics of BPTI, conformational change pairs, and intrinsically disordered proteins. SLM provides a highly efficient solution, offering a 20-100x speedup than existing methods in generating diverse conformations, shedding light on promising avenues for future research. |
| title | Structure Language Models for Protein Conformation Generation |
| topic | Biomolecules Machine Learning |
| url | https://arxiv.org/abs/2410.18403 |