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(1997 Dahiyat & Mayo) De novo protein design using fully automated sequence selection

A novel sequence for an entire protein was produced using fully automated design and then experimentally validated by nuclear magnetic resonance spectroscopy. The computational design algorithm used physical chemical potential functions and stereochemical constraints to search among 1.9 x 10(27) possible amino acid sequences for compatibility with the polypeptide backbone structure of a zinc finger domain. The resulting structure was compact, well-ordered, and had little similarity to any known protein sequence. Containing only 28 amino-acid monomers, it was the smallest protein known to be capable of folding into a unique structure without the assistance of disulfide bonds, coordinated metal ions, or the like. This result demonstrated that automated computational methods can perform the combinatorial search required for protein design.

With link to abstract:

Dahiyat, BI and Mayo, SL, “De Novo Protein Design: Fully Automated Sequence Selection,” Science 1997 278: 82-87.