{"id":17600,"date":"2022-11-30T23:27:30","date_gmt":"2022-12-01T04:27:30","guid":{"rendered":"https:\/\/d3.harvard.edu\/platform-digit\/?post_type=hck-submission&p=17600"},"modified":"2022-11-30T23:28:24","modified_gmt":"2022-12-01T04:28:24","slug":"protein-origami-can-deepminds-alphafold-revolutionize-drug-discovery","status":"publish","type":"hck-submission","link":"https:\/\/d3.harvard.edu\/platform-digit\/submission\/protein-origami-can-deepminds-alphafold-revolutionize-drug-discovery\/","title":{"rendered":"Protein Origami: Can DeepMind\u2019s AlphaFold revolutionize drug discovery?"},"content":{"rendered":"\n\n\n

What is a protein and why is it important?
<\/strong>In recent years, mRNA has been the most talked about biochemical molecule, bolstered by the sequencing and open source nature of the human genome and technologies like CRISPR. Much like a genome, all living organisms also have a proteome, which details all of the proteins that can be made by a cell or organism. Proteins in the human body \u201cprovide structure, produce energy, as well as allow communication, movement, and reproduction\u201d . For example, proteins in the human body include keratin, which provide the structure of hair and nails, Immunoglobulin G, the most common antibody in blood, and Insulin, a hormone that regulates blood glucose to name just a few.
In effect, proteins are found everywhere in the human body; unfortunately, protein misfolding is \u201cbelieved to be the primary cause of Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Creutzfeldt-Jakob disease, cystic fibrosis, Gaucher’s disease and many other degenerative and neurodegenerative disorders.\u201d<\/p>\n\n\n\n

The Hard Problem
<\/strong>Each protein is comprised of a chain of amino acids (protein building blocks), of which there are 20 unique ones found in most biological life. This chain commonly has 50 individual amino acid beads, and can have as many as 10^300 different configurations . This is due to the myriad combinations of amino acids and their unique chemistry which combine different atomic shapes and create areas of polarity. This is in contrast to nucleic acids, which only have 5 nucleotides (DNA\/RNA building blocks), and due to their unique chemistry, always take on the classic double-helix spiral.<\/p>\n\n\n\n


The number of combinations alone make protein folding a quantitatively difficult problem to solve, but the method of observing proteins is also a challenge due to their ability to denature (\u201cunfold\u201d) in different environments, and the methods currently available to observe their true forms (X-Ray Crystallography). The non-AI methods were laborious, expensive, and could take years of research. One way to think about it: a blob fish is so named because that\u2019s how it looks out of the ocean depths where it resides. But in the deep ocean, a blob fish looks completely different. This is much the same problem that protein folding faces, in that it is difficult to observe the protein in situ and to understand how and where it functions.<\/p>\n\n\n\n

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Figure 1: A Picture is worth a thousand words – the blobfish represents the one aspect of the challenge of visualizing proteins under technology constraints.
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AlphaFold AI<\/strong>
Deepmind, a subsidiary of Google, set out to solve the hard problem of understanding how all 200 million known proteins fold, using AI in place of traditional scientific tools of measurement.
Timeline:<\/p>\n\n\n\n