Multiply-Entangled De Novo Proteins (#375)
Abstract:
Entangled molecules have captured the attention of chemists because of both their aesthetic appeal and their potential use as molecular machines.1To date, most entangled molecules made in the lab are built from either artificial building blocks2–4 or DNA.5,6 Controlling the level of entanglement of other biomolecules, such as proteins, would allow chemists to build new sophisticated molecular machines that could be directly expressed and operated in living cells. Although entanglements naturally occur in certain proteins,7 it has proved challenging to identify the sequences of amino acid correlating with the. presence of entanglements. As a result, it is currently not possible to design de novo protein knots. The hydrophobic effect is utilized to drive the peptides and coavalent linking for the higher order architeture formations (folding into a knot) Rather than screening a large number of protein sequences, which would be extremely time consuming, we will design a dynamic combinatorial system8 from which knotted proteins will be naturally selected and amplified.
Figure . General principle for the assembly of multiply-entangled proteins.
References
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