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journal article·2025-12Open access

Integration of Generative Protein Design with Synthetic Porphyrin Assembly: Metal‐Responsive Cyclic Assembly of a Bi‐Porphyrin Acquisition Designer Protein

Hiroaki Inaba, Hiroki Onoda, Takayuki Uchihashi, Atsunori Oshima, Osami Shoji

Small· Volume 21· Issue 49
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Abstract

Abstract De novo protein design has been used to create functional protein assemblies, but its reliance on standard amino acids limits the integration of synthetic supramolecular strategies for precise control of molecular assemblies. Herein, an artificial protein assembly that integrates synthetic supramolecular design with de novo protein engineering is presented. Focusing on unit and connection rigidity, the Bi‐Porphyrin Acquisition Designer protein (BiPAD), which captures two synthetic porphyrin molecules via state‐of‐the‐art generative protein design to fuse α/β‐folded porphyrin‐binding motifs, is designed and created. BiPADs captures rigid porphyrins, each bearing an additional metal coordination site, resulting in a metal‐responsive cyclic assembly with the intended structure. Furthermore, high‐speed atomic force microscopy reveals dynamic structural changes in the BiPAD assembly. This work expands the designability of artificial protein assemblies, paving the way for the synergistic design of functional systems through the integration of protein engineering and synthetic chemistry.
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Research context

OpenAlex topics: Supramolecular Chemistry and Complexes · Supramolecular Self-Assembly in Materials · Chemical Synthesis and Analysis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Chemistry School of Science Nagoya University Furo‐cho, Chikusa‐ku Nagoya Aichi 464‐0802 Japan

AICHI SR Center Nagoya University Minamiyamaguchi‐cho Nagoya Aichi 464‐8603 Japan

Exploratory Research Center on Life and Living Systems National Institutes of Natural Sciences Okazaki 444‐8787 Japan

Institute for Glyco‐core Research (iGCORE) Nagoya University Nagoya Aichi 464‐0814 Japan

Department of Physics School of Science Nagoya University Furo‐cho, Chikusa‐ku Nagoya Aichi 464‐0802 Japan

Cellular and Structural Physiology Institute (CeSPI) Nagoya University Furo‐cho, Chikusa‐ku Nagoya Aichi 464‐8601 Japan

Department of Basic Medicinal Sciences Graduate School of Pharmaceutical Sciences Nagoya University Furo‐cho, Chikusa‐ku Nagoya Aichi 464‐8601 Japan

Center for One Medicine Innovative Translational Research (COMIT) Gifu University Institute for Advanced Study Gifu 501‐11193 Japan

Research Institute for Quantum and Chemical Innovation Institutes of Innovation for Future Society Nagoya University Furo‐cho, Chikusa‐ku Nagoya 461‐8601 Japan

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