This is a wish list for protein folding and engineering. It contains some speculation and brain storming and shouldn't be considered completely viable for now.

Wishlist

  • Given a 3d shape (of some nanostructure), produce a protein's amino acid sequence that will consistently create that shape. (done as of 2023?)

  • Control over protein functional properties, such as catalytic domains and sites, as well as designing specific confirmational changes and control over conformation changes.

  • DNA data storage: faster polymerases

  • Proteins that make molecular display techniques easier (simplifying lab bench protocols) -- like mRNA display and ribosome display; easier molecular display would be very valuable for projects using directed evolution techniques.

  • Better protein-based nanopores for DNA sequencing, amino acid sequencing, and protein sensing.

  • Human-controlled DNA polymerase synthesis activity (choose each nucleotide), or an instrumented ribosome to control protein production regardless of mRNA content

  • Molecular protein lego: connect multiple legos together to build large-scale protein structures. This is generally useful for modeling and nanostructures. Binding by DNA addresses or other high affinity ligand specific techniques, for a stable toolbox of known protein structures and shapes and building up larger structures from small parts.

  • Protein mechanical logic: protein structures that have internal logic and state, based on mechanical motion or other catalytic reactions and interactions.

  • Generalized, fully-programmable molecular nanotechnology: programmable nanomachines and nanofactories that can produce other nanostructures to exact specifications, without uncertainty regarding protein folding.

TODO

  • What were those long-tube protein molecular-chemistry factories called? (non-ribosomal peptide synthetases or NRPS). They are apparently natural, and they have multiple points of interest inside the tube that modify a molecule as it progresses along the protein.

Other interesting targets

  • gene editing proteins (see gene-editing)
  • enzymes for DNA synthesis
  • molecular recording (like in vivo DNA-based recording devices, for debugging or otherwise, lineage tracing techniques, "of toasters and molecular ticker tapes")
  • protein binding affinity stuff (protein-protein interaction)
  • catalytic activity, enhancement of catalysis or reduction of catalysis
  • synthetic metabolisms
  • biosensors

Structural protein design with machine learning

Well, it's probably time to update this page... lots of recent progress in machine learning for protein design.

References

See https://diyhpl.us/~bryan/papers2/bio/protein-engineering/