De novo design of small molecule–regulated protein oligomers

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Source: Science Magazine

Original: https://www.science.org/doi/abs/10.1126/science.ady6017?af=R...

Published: 2026-01-01T08:00:00Z

Scientists have developed a computational "docking-while-binding" method to de novo design protein homooligomers regulated by small molecules with the corresponding symmetry.1 This method simultaneously optimizes protein-protein and protein-ligand interactions during docking, creating one or more ligand binding sites directly at the protein interface.Previous approaches relied on existing structural information and were limited to heterodimers.[The method allowed the creation of homotrimers, heterodimers, and heterotrimers regulated by amantadine, which they validated in cellular and animal models.1 The protein components have a compact size of approximately 65 amino acids and utilize an FDA-approved orally administered small molecule.[The system is suitable for translational applications in biotechnology and cell therapies.1 The approach extends the chemogenetic toolbox to manipulate biological processes with high temporal precision[1].