PB-GPT:基于 GPT 的创新型蛋白质骨架生成模型

IF 4.4 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Structure Pub Date : 2024-08-21 DOI:10.1016/j.str.2024.07.016
Xiaoping Min, Yiyang Liao, Xiao Chen, Qianli Yang, Junjie Ying, Jiajun Zou, Chongzhou Yang, Jun Zhang, Shengxiang Ge, Ningshao Xia
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引用次数: 0

摘要

利用先进的计算方法,现在可以修改或设计蛋白质以实现特定功能,这一过程对疾病治疗和其他医学应用具有重要意义。蛋白质的结构和功能与其骨架有着内在联系,因此骨架的设计是蛋白质工程的关键环节。本研究的重点是无条件生成蛋白质骨架。通过编码本量化和压缩字典,我们将蛋白质骨架结构转换为一种独特的编码语言,并提出了基于 GPT 的蛋白质骨架生成模型 PB-GPT。为了验证模型的泛化性能,我们在公共数据集和小型蛋白质数据集上对模型进行了训练和评估。结果表明,我们的模型能够无条件生成精细、高度逼真的蛋白质骨架,其结构模式与天然蛋白质相似,从而展示了大语言模型在蛋白质结构设计中的巨大潜力。
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PB-GPT: An innovative GPT-based model for protein backbone generation

With advanced computational methods, it is now feasible to modify or design proteins for specific functions, a process with significant implications for disease treatment and other medical applications. Protein structures and functions are intrinsically linked to their backbones, making the design of these backbones a pivotal aspect of protein engineering. In this study, we focus on the task of unconditionally generating protein backbones. By means of codebook quantization and compression dictionaries, we convert protein backbone structures into a distinctive coded language and propose a GPT-based protein backbone generation model, PB-GPT. To validate the generalization performance of the model, we trained and evaluated the model on both public datasets and small protein datasets. The results demonstrate that our model has the capability to unconditionally generate elaborate, highly realistic protein backbones with structural patterns resembling those of natural proteins, thus showcasing the significant potential of large language models in protein structure design.

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来源期刊
Structure
Structure 生物-生化与分子生物学
CiteScore
8.90
自引率
1.80%
发文量
155
审稿时长
3-8 weeks
期刊介绍: Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome. In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.
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