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Updated: Sep 26, 2026

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
De novo design of foldable proteins with smooth folding funnel: automated negative design and experimental
Wenzhen Jin1, Ohki Kambara, Hiroaki Sasakawa
1Graduate School of Science and Technology, Japan Science and Technology Corporation, Kobe University, Rokkodai, Nada, 657-8501, Kobe, Japan.
Abstract:
De novo sequence design of foldable proteins provides a way of investigating principles of protein architecture. We performed fully automated sequence design for a target structure having a three-helix bundle topology and synthesized the designed sequences. Our design principle is different from the conventional approach, in that instead of optimizing interactions within the target structure, we design the global shape of the protein folding funnel. This includes automated implementation of negative design by explicitly requiring higher free energy of the denatured state. The designed sequences do not have significant similarity to those of any natural proteins. The NMR and CD spectroscopic data indicated that one designed sequence has a well-defined three-dimensional structure as well as alpha-helical content consistent with the target.
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