DOE OSTI · 3031160
Bond-centric modular design of protein assemblies
Abstract
Directional interactions that generate regular coordination geometries are a powerful means of guiding molecular and colloidal self-assembly, but implementing such high-level interactions with proteins remains challenging due to their complex shapes and intricate interface properties. Here we describe a modular approach to protein nanomaterial design inspired by the rich chemical diversity that can be generated from the small number of atomic valencies. We design protein building blocks using deep learning-based generative tools, incorporating regular coordination geometries and tailorable bonding interactions that enable the assembly of diverse closed and open architectures guided by simple geometric principles. Experimental characterization confirms the successful formation of more than 20 multicomponent polyhedral protein cages, two-dimensional arrays and three-dimensional protein lattices, with a high (10%–50%) success rate and electron microscopy data closely matching the corresponding design models. Due to modularity, individual building blocks can assemble with different partners to generate distinct regular assemblies, resulting in an economy of parts and enabling the construction of reconfigurable networks for designer nanomaterials.
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Wang, Shunzhi [University of Washington, Seattle, WA (United States)] (ORCID:0000000150337478), Favor, Andrew [University of Washington, Seattle, WA (United States)] (ORCID:0000000299772785), Kibler, Ryan D. [University of Washington, Seattle, WA (United States)] (ORCID:0000000169849887), Lubner, Joshua M. [University of Washington, Seattle, WA (United States)] (ORCID:0000000315060949), Borst, Andrew J. [University of Washington, Seattle, WA (United States)] (ORCID:0000000342977824), Coudray, Nicolas [Johns Hopkins University, Baltimore, MD (United States); NYU Grossman School of Medicine, New York, NY (United States)] (ORCID:0000000260502219), Redler, Rachel L. [Johns Hopkins University, Baltimore, MD (United States)] (ORCID:0000000306211303), Chiang, Huat Thart [University of Washington, Seattle, WA (United States)] (ORCID:0000000200427958), Sheffler, William [University of Washington, Seattle, WA (United States)], Hsia, Yang [University of Washington, Seattle, WA (United States)] (ORCID:0000000174678373), Bethel, Neville P. [University of Washington, Seattle, WA (United States)], Li, Zhe [University of Washington, Seattle, WA (United States)], Ekiert, Damian C. [Johns Hopkins University, Baltimore, MD (United States)], Bhabha, Gira [Johns Hopkins University, Baltimore, MD (United States)] (ORCID:0000000306246178), Pozzo, Lilo D. [University of Washington, Seattle, WA (United States)] (ORCID:0000000171049061), Baker, David [University of Washington, Seattle, WA (United States)] (ORCID:0000000178966217). 2025-07-31. Bond-centric modular design of protein assemblies. https://doi.org/10.1038/s41563-025-02297-5
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