RFdiffusion: Diffusion model generates protein backbones
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Re: RFdiffusion: Diffusion model generates protein backbones
#2So I guess this means easier drug discovery? Honesty those wiggly diagrams are meaningless to me I have no bio background
Re: RFdiffusion: Diffusion model generates protein backbones
#3So I guess this means easier drug discovery? Honesty those wiggly diagrams are meaningless to me I have no bio background
Easier drug discovery is what they tell public and grant agencies. In a roundabout way it’s true. Maybe. Many other hurdles still exist. But what this and other similar tools really are, is significantly advancing basic science in creating our own protein designs.
Before alphafold changed this field, creating your own protein design was considered an insane task (not impossible, bakers lab and others have done it a couple times). But these tools (now we have multiple) allow you to create new proteins From scratch that can do exactly what you want (caveats galore). New enzymes that can catalyze reactions never found in nature for example.
Before this all we could do was take proteins that already exist in nature and modify them. So you can imagine how new this world is.
Re: RFdiffusion: Diffusion model generates protein backbones
#4So I guess this means easier drug discovery? Honesty those wiggly diagrams are meaningless to me I have no bio background
Easier drug discovery is what they tell public and grant agencies. In a roundabout way it’s true. Maybe. Many other hurdles still exist. But what this and other similar tools really are, is significantly advancing basic science in creating our own protein designs. Before alphafold changed this field, creating your own protein design was considered an insane task (not impossible, bakers lab and others have done it a c…
Large Language models can also generate novel and working protein structures that adhere to a specified purpose
https://www.nature.com/articles/s41587-022-01618-2
Re: RFdiffusion: Diffusion model generates protein backbones
#5Earlier quoted context omitted.
Easier drug discovery is what they tell public and grant agencies. In a roundabout way it’s true. Maybe. Many other hurdles still exist. But what this and other similar tools really are, is significantly advancing basic science in creating our own protein designs. Before alphafold changed this field, creating your own protein design was considered an insane task (not impossible, bakers lab and others have done it a c…
Large Language models can also generate novel and working protein structures that adhere to a specified purpose https://www.nature.com/articles/s41587-022-01618-2
Can optical tweezers construct such proteins; or is there a more efficient way?
Optical tweezers: https://en.wikipedia.org/wiki/Optical_tweezers
"'Impossible' photonic breakthrough: scientist manipulate light at subwavelength scale" https://thedebrief.org/impossible-photonic-breakthrough-scie... :
> have successfully demonstrated that a beam of light can not only be confined to a spot that is 50 times smaller than its own wavelength but also “in a first of its kind” the spot can be moved by minuscule amounts at the point where the light is confined.
> According to that research, the key to confining light below the previous impermeable Abbe diffraction limit was accomplished by “storing a part of the electromagnetic energy in the kinetic energy of electric charges.” This clever adaptation, the researchers wrote, “opened the door to a number of groundbreaking real-world applications, which has contributed to the great success of the field of nanophotonics.”
> “Looking to the future, in principle, it could lead to the manipulation of micro and nanometre-sized objects, including biological particles,” De Liberato says, “or perhaps the sizeable enhancement of the sensitivity resolution of microscopic sensors.”
"Digging into DNA Repair with Optical Tweezer Technology" https://www.genengnews.com/topics/digging-into-dna-repair-wi...
Re: RFdiffusion: Diffusion model generates protein backbones
#6Corresponding paper to RFdiffusion: https://www.biorxiv.org/content/10.1101/2022.12.09.519842v2
Some context: Been waiting for this to come out for a while! Main innovation is leveraging RosettaFold (protein folding neural net) to generate protein backbones via diffusing in 3D space! From backbones, we can generate sequences that would fold into said structures via sequence design algorithms (check out: proteinMPNN, Rosetta FastDesign).
In terms of applications: This is super relevant for our ability to create strongly binding protein binders (ex timely creation of proteins that bind to virus spike proteins), and designing enzyme from scratch!
Prior methods suffered from much lower success rates for generating “good” backbone structures. Extremely exciting!! If you want to learn more, check out the Baker group at UW!
Re: RFdiffusion: Diffusion model generates protein backbones
#7Earlier quoted context omitted.
Large Language models can also generate novel and working protein structures that adhere to a specified purpose https://www.nature.com/articles/s41587-022-01618-2
Can optical tweezers construct such proteins; or is there a more efficient way? Optical tweezers: https://en.wikipedia.org/wiki/Optical_tweezers "'Impossible' photonic breakthrough: scientist manipulate light at subwavelength scale" https://thedebrief.org/impossible-photonic-breakthrough-scie... : > have successfully demonstrated that a beam of light can not only be confined to a spot that is 50 times smaller than it…
It's much easier than that! Living cells already have ribosomes that construct proteins and all the other molecular machinery needed to go from DNA sequence to assembled protein. You can order a DNA sequence online and put it into e-coli or yeast cells and those cells will make that protein for you.
Re: RFdiffusion: Diffusion model generates protein backbones
#8Earlier quoted context omitted.
Can optical tweezers construct such proteins; or is there a more efficient way? Optical tweezers: https://en.wikipedia.org/wiki/Optical_tweezers "'Impossible' photonic breakthrough: scientist manipulate light at subwavelength scale" https://thedebrief.org/impossible-photonic-breakthrough-scie... : > have successfully demonstrated that a beam of light can not only be confined to a spot that is 50 times smaller than it…
It's much easier than that! Living cells already have ribosomes that construct proteins and all the other molecular machinery needed to go from DNA sequence to assembled protein. You can order a DNA sequence online and put it into e-coli or yeast cells and those cells will make that protein for you.
TIL about mail-order CRISPR kits. "Mail-Order CRISPR Kits Allow Absolutely Anyone to Hack DNA" (2017) https://www.scientificamerican.com/article/mail-order-crispr...
Protein production: https://en.wikipedia.org/wiki/Protein_production
Tissue Nanotransfection reprograms e.g. fibroblasts into neurons and endothelial cells (for ischemia) using electric charge. Are there different proteins then expressed? Which are the really useful targets?
> The delivered cargo then transforms the affected cells into a desired cell type without first transforming them to stem cells. TNT is a novel technique and has been used on mice models to successfully transfect fibroblasts into neuron-like cells along with rescue of ischemia in mice models with induced vasculature and perfusion
> [...] This chip is then connected to an electrical source capable of delivering an electrical field to drive the factors from the reservoir into the nanochannels, and onto the contacted tissue
https://en.wikipedia.org/wiki/Tissue_nanotransfection#Techni...
Are there lab safety standards for handling yeast or worse? https://en.wikipedia.org/wiki/Gene_drive
Re: RFdiffusion: Diffusion model generates protein backbones
#9Can stuff like this be used for other polymers, like thermoplastics? Can you speed up molecular modeling of thermoplastic crystallization?
Re: RFdiffusion: Diffusion model generates protein backbones
#10Earlier quoted context omitted.
Can optical tweezers construct such proteins; or is there a more efficient way? Optical tweezers: https://en.wikipedia.org/wiki/Optical_tweezers "'Impossible' photonic breakthrough: scientist manipulate light at subwavelength scale" https://thedebrief.org/impossible-photonic-breakthrough-scie... : > have successfully demonstrated that a beam of light can not only be confined to a spot that is 50 times smaller than it…
It's much easier than that! Living cells already have ribosomes that construct proteins and all the other molecular machinery needed to go from DNA sequence to assembled protein. You can order a DNA sequence online and put it into e-coli or yeast cells and those cells will make that protein for you.
That’s like saying anyone who has a computer can hack into the NSA. In principle yes, but the amount of know-how and troubleshooting is being underplayed here. Not to mention the question of what you do with the protein once you produce it.