101-Computational Design of Specific DNA-Binding Proteins
This article details a novel computational method for designing sequence-specific DNA-binding proteins (DBPs), which are crucial tools in biotechnology and gene editing. The researchers developed a pipeline, incorporating tools like RIFdock and LigandMPNN, to generate small DBPs that can recognize arbitrary DNA sequences, a challenge unmet by previous computational redesign efforts. Experimental validation via yeast display and biolayer interferometry confirmed that the designed DBPs bind their target sequences with mid-to-high nanomolar affinity and high specificity, with a solved crystal…
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