Accessible PDF of Nature paper

This is great - sounds like it has enormous potential! Is a future step to make the gate at the entrance controllable (to allow release of a drug at the desired time, for example), or is that already possible?

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Yet another paper from the Baker lab - this time in Science!

I last posted about Yang Hsia's work designing an icosahedron from a single protein subunit that could be used to deliver drugs or to develop powerful new vaccines. In new work published last week, Baker lab scientists and collaborators have taken this work to an exciting new level by engineering 120-subunit icosahedral nanocages that self-assemble from not one, but two distinct protein components. The advantage of having two components is the ability to control assembly of the nanoparticle by mixing the individually prepared subunits.

The new designed proteins are described in the latest issue of Science in a paper entitled “Accurate design of megadalton-scale multi-component icosahedral protein complexes”.

Here is a link to the IPD news post about the work. It also contains links to other articles about this exciting work.

Science did a great profile on David Baker and protein design which you can read here.

Accompanying video on protein folding and design here!

Yet another paper from the Baker lab - this time in Science!

I last posted about Yang Hsia's work designing an icosahedron from a single protein subunit that could be used to deliver drugs or to develop powerful new vaccines. In new work published last week, Baker lab scientists and collaborators have taken this work to an exciting new level by engineering 120-subunit icosahedral nanocages that self-assemble from not one, but two distinct protein components. The advantage of having two components is the ability to control assembly of the nanoparticle by mixing the individually prepared subunits.

The new designed proteins are described in the latest issue of Science in a paper entitled “Accurate design of megadalton-scale multi-component icosahedral protein complexes”.

Here is a link to the IPD news post about the work. It also contains links to other articles about this exciting work.

Science did a great profile on David Baker and protein design which you can read here.

Accompanying video on protein folding and design here!

wow, this is really big. Thanks for the update!

Research Update:

We recently published an article in Nature titled "Accurate de novo design of hyperstable constrained peptides". We would like to thank all Rosetta@Home participants for their help with this work. In the paper, we present computational methods for designing small stapled peptides with exceptional stabilities. These methods and designed peptides provide platform for rational design of new peptide-based therapeutics. Constrained (stapled) peptides combine the stability of conventional small-molecule drugs with the selectivity and potency of antibody therapeutics. Ability to precisely design these peptides in custom shapes and sizes opens up possibilities for "on-demand" design of peptide-based therapeutics.

Other developments describe in the paper:

1) We can now accurately design 18-47 amino acid peptides that incorporate multiple cross-links.
2) We can now design peptides that incorporate unnatural amino acids. Specifically, we designed peptides with a mix of natural L-amino amino acids and D-amino acids (mirror images of L-amino acids). D-amino acids tend to provide better protease resistance and lower immunogenicity; both of which are desired properties in a therapeutic peptide. Unnatural amino acids also let us sample much more diverse shapes and functions.
3) We can now design peptides that are cyclized via a peptide bond between their N- and C-terminus. Cyclic peptides provide increased resistance against exopeptidases as they have no free ends, and thus are ideal candidates for engineering peptide therapeutics.

We are now working to use these computational methods for designing peptides that target therapeutically relevant targets, such as, enzymes that impart antibiotic resistance in pathogenic bacteria.

Structure prediction runs on Rosetta@Home for these designed peptide models played a key role in selection of good designs that were experimentally synthesized and characterized. So, thanks a lot to all of you for your help in making this work possible.

Research Update:

We recently published an article in Nature titled "Accurate de novo design of hyperstable constrained peptides". We would like to thank all Rosetta@Home participants for their help with this work. In the paper, we present computational methods for designing small stapled peptides with exceptional stabilities. These methods and designed peptides provide platform for rational design of new peptide-based therapeutics. Constrained (stapled) peptides combine the stability of conventional small-molecule drugs with the selectivity and potency of antibody therapeutics. Ability to precisely design these peptides in custom shapes and sizes opens up possibilities for "on-demand" design of peptide-based therapeutics.

Other developments describe in the paper:

1) We can now accurately design 18-47 amino acid peptides that incorporate multiple cross-links.
2) We can now design peptides that incorporate unnatural amino acids. Specifically, we designed peptides with a mix of natural L-amino amino acids and D-amino acids (mirror images of L-amino acids). D-amino acids tend to provide better protease resistance and lower immunogenicity; both of which are desired properties in a therapeutic peptide. Unnatural amino acids also let us sample much more diverse shapes and functions.
3) We can now design peptides that are cyclized via a peptide bond between their N- and C-terminus. Cyclic peptides provide increased resistance against exopeptidases as they have no free ends, and thus are ideal candidates for engineering peptide therapeutics.

We are now working to use these computational methods for designing peptides that target therapeutically relevant targets, such as, enzymes that impart antibiotic resistance in pathogenic bacteria.

Structure prediction runs on Rosetta@Home for these designed peptide models played a key role in selection of good designs that were experimentally synthesized and characterized. So, thanks a lot to all of you for your help in making this work possible.

Gaurav, do any of those new peptides include BMAA? That amino acid is normally found only in blue-green algae and in cyanobacteria, but has also been found in the brains of many Alzheimer's victims. Look for papers on recent Nobel prizes if you need more details.

感觉很高大尚，尽一份力…