Multi-scale structural similarity embedding search across entire proteomes.

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Tác giả: Sebastian Bittrich, Stephen K Burley, Jose M Duarte, Yana Rose, Ruben Sanchez-Garcia, Joan Segura

Ngôn ngữ: eng

Ký hiệu phân loại: 796.5423 Outdoor life

Thông tin xuất bản: United States : bioRxiv : the preprint server for biology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 723395

The rapid expansion of three-dimensional (3D) biomolecular structure information, driven by breakthroughs in artificial intelligence/deep learning (AI/DL)-based structure predictions, has created an urgent need for scalable and efficient structure similarity search methods. Traditional alignment-based approaches, such as structural superposition tools, are computationally expensive and challenging to scale with the vast number of available macromolecular structures. Herein, we present a scalable structure similarity search strategy designed to navigate extensive repositories of experimentally determined structures and computed structure models predicted using AI/DL methods. Our approach leverages protein language models and a deep neural network architecture to transform 3D structures into fixed-length vectors, enabling efficient large-scale comparisons. Although trained to predict TM-scores between single-domain structures, our model generalizes beyond the domain level, accurately identifying 3D similarity for full-length polypeptide chains and multimeric assemblies. By integrating vector databases, our method facilitates efficient large-scale structure retrieval, addressing the growing challenges posed by the expanding volume of 3D biostructure information.
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