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Accurate and efficient protein sequence design through learning concise local environment of residues
Accurate and efficient protein sequence design through learning concise local environment of residues
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Accurate and efficient protein sequence design through learning concise local environment of residues
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Accurate and efficient protein sequence design through learning concise local environment of residues
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Accurate and efficient protein sequence design through learning concise local environment of residues
Accurate and efficient protein sequence design through learning concise local environment of residues
Paper

Accurate and efficient protein sequence design through learning concise local environment of residues

2022
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Overview
Protein sequence design has been widely applied in rational protein engineering and increasing the design accuracy and efficiency is highly desired. Here we present ProDESIGN-LE, an accurate and efficient design approach, which adopts a concise but informative representation of residue's local environment and trains a transformer to select an appropriate residue at a position from its local environment. ProDESIGN-LE iteratively applies the transformer on the positions in the target structure, eventually acquiring a designed sequence with all residues fitting well with their local environments. ProDESIGN-LE designed sequences for 68 naturally occurring and 129 hallucinated proteins within 20 seconds per protein on average, and the predicted structures from the designed sequences perfectly resemble the target structures with state-of-the-art average TM-score exceeding 0.80. We further experimentally validated ProDESIGN-LE by designing five sequences for an enzyme, chloramphenicol O-acetyltransferase type III (CAT III), and recombinantly expressing the proteins in E. coli. Of these proteins, three exhibited excellent solubility, and one yielded monomeric species with circular dichroism spectra consistent with the natural CAT III protein. Competing Interest Statement The authors have declared no competing interest. Footnotes * None