8XYS

De novo designed protein GPX4-1

8XYS の概要

• エントリーDOI: 10.2210/pdb8xys/pdb
• 分子名称: De novo designed GPX4-1 (2 entities in total)
• 機能のキーワード: de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 80672.84

構造登録者

Liu, J.L.,Guo, Z.,Lai, L.H. (登録日: 2024-01-20, 公開日: 2024-10-02, 最終更新日: 2025-04-23)

主引用文献

Liu, J.,Guo, Z.,You, H.,Zhang, C.,Lai, L.
All-Atom Protein Sequence Design Based on Geometric Deep Learning.
Angew.Chem.Int.Ed.Engl., 63:e202411461-e202411461, 2024

PubMed Abstract: Designing sequences for specific protein backbones is a key step in creating new functional proteins. Here, we introduce GeoSeqBuilder, a deep learning framework that integrates protein sequence generation with side chain conformation prediction to produce the complete all-atom structures for designed sequences. GeoSeqBuilder uses spatial geometric features from protein backbones and explicitly includes three-body interactions of neighboring residues. GeoSeqBuilder achieves native residue type recovery rate of 51.6 %, comparable to ProteinMPNN and other leading methods, while accurately predicting side chain conformations. We first used GeoSeqBuilder to design sequences for thioredoxin and a hallucinated three-helical bundle protein. All the 15 tested sequences expressed as soluble monomeric proteins with high thermal stability, and the 2 high-resolution crystal structures solved closely match the designed models. The generated protein sequences exhibit low similarity (minimum 23 %) to the original sequences, with significantly altered hydrophobic cores. We further redesigned the hydrophobic core of glutathione peroxidase 4, and 3 of the 5 designs showed improved enzyme activity. Although further testing is needed, the high experimental success rate in our testing demonstrates that GeoSeqBuilder is a powerful tool for designing novel sequences for predefined protein structures with atomic details. GeoSeqBuilder is available at https://github.com/PKUliujl/GeoSeqBuilder.

PubMed: 39295564
DOI: 10.1002/anie.202411461

実験手法

X-RAY DIFFRACTION (2.2 Å)