8HDU

De novo design cavitated protein without predefined topology

Summary for 8HDU

• Entry DOI: 10.2210/pdb8hdu/pdb
• Descriptor: De novo design cavitated protein (2 entities in total)
• Functional Keywords: de novo design, cavitated protein, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 5
• Total formula weight: 114911.47

Authors

Hu, X.,Xu, Y. (deposition date: 2022-11-06, release date: 2023-01-18, Last modification date: 2024-04-24)

Primary citation

Xu, Y.,Hu, X.,Wang, C.,Liu, Y.,Chen, Q.,Liu, H.
De novo design of cavity-containing proteins with a backbone-centered neural network energy function.
Structure, 32:424-, 2024

PubMed Abstract: The design of small-molecule-binding proteins requires protein backbones that contain cavities. Previous design efforts were based on naturally occurring cavity-containing backbone architectures. Here, we designed diverse cavity-containing backbones without predefined architectures by introducing tailored restraints into the backbone sampling driven by SCUBA (Side Chain-Unknown Backbone Arrangement), a neural network statistical energy function. For 521 out of 5816 designs, the root-mean-square deviations (RMSDs) of the Cα atoms for the AlphaFold2-predicted structures and our designed structures are within 2.0 Å. We experimentally tested 10 designed proteins and determined the crystal structures of two of them. One closely agrees with the designed model, while the other forms a domain-swapped dimer, where the partial structures are in agreement with the designed structures. Our results indicate that data-driven methods such as SCUBA hold great potential for designing de novo proteins with tailored small-molecule-binding function.

PubMed: 38325370
DOI: 10.1016/j.str.2024.01.006

Experimental method

X-RAY DIFFRACTION (2.71 Å)