7DKK

De novo design protein XM2H

7DKK の概要

• エントリーDOI: 10.2210/pdb7dkk/pdb
• 分子名称: De novo design protein XM2H (2 entities in total)
• 機能のキーワード: monomer, ferredoxin-like, 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: 37594.66

構造登録者

Bin, H. (登録日: 2020-11-24, 公開日: 2021-12-08, 最終更新日: 2024-05-29)

主引用文献

Huang, B.,Xu, Y.,Hu, X.,Liu, Y.,Liao, S.,Zhang, J.,Huang, C.,Hong, J.,Chen, Q.,Liu, H.
A backbone-centred energy function of neural networks for protein design.
Nature, 602:523-528, 2022

PubMed Abstract: A protein backbone structure is designable if a substantial number of amino acid sequences exist that autonomously fold into it. It has been suggested that the designability of backbones is governed mainly by side chain-independent or side chain type-insensitive molecular interactions, indicating an approach for designing new backbones (ready for amino acid selection) based on continuous sampling and optimization of the backbone-centred energy surface. However, a sufficiently comprehensive and precise energy function has yet to be established for this purpose. Here we show that this goal is met by a statistical model named SCUBA (for Side Chain-Unknown Backbone Arrangement) that uses neural network-form energy terms. These terms are learned with a two-step approach that comprises kernel density estimation followed by neural network training and can analytically represent multidimensional, high-order correlations in known protein structures. We report the crystal structures of nine de novo proteins whose backbones were designed to high precision using SCUBA, four of which have novel, non-natural overall architectures. By eschewing use of fragments from existing protein structures, SCUBA-driven structure design facilitates far-reaching exploration of the designable backbone space, thus extending the novelty and diversity of the proteins amenable to de novo design.

PubMed: 35140398
DOI: 10.1038/s41586-021-04383-5

実験手法

X-RAY DIFFRACTION (2.1 Å)