AlphaFold: The making of a scientific breakthrough

The inside story of the DeepMind team of scientists and engineers who created AlphaFold, an AI system that is recognised as a solution to "protein folding", a grand scientific challenge for more than 50 years.

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Protein references:
TBP = To be published

1BYI: Sandalova, T., et al. (1999) Structure of dethiobiotin synthetase at 0.97 A resolution. Acta Crystallographica Section D 55: 610-624.
3NPD: Das, D. et al. (2014) Crystal structure of a putative quorum sensing-regulated protein (PA3611) from the Pseudomonas-specific DUF4146 family. Proteins 82: 1086-1092.
5AOZ: Bule, P., et al. Structural Characterization of the Third Cohesin from Ruminococcus Flavefaciens Scaffoldin Protein, Scab. (TBP)
5ERE: Joachimiak, A. A novel extracellular ligand receptor. (TBP)
5L8E: Dharadhar, S., et al. (2016) A conserved two-step binding for the UAF1 regulator to the USP12 deubiquitinating enzyme. Journal of Structural Biology 196: 437-447.
5M20: Liauw, P., et al. Structure of Thermosynechococcus elongatus Psb32 fused to sfGFP. (TBP)
5W9F: Buchko, G.W., et al. (2018) Cytosolic expression, solution structures, and molecular dynamics simulation of genetically encodable disulfide-rich de novo designed peptides. Protein Science 27: 1611-1623.
6BTC: Mir-Sanchis, I., et al. (2018) Crystal Structure of an Unusual Single-Stranded DNA-Binding Protein Encoded by Staphylococcal Cassette Chromosome Elements. Structure 26: 1144.
6CL6: Buth, S.A., et al. (2018) Structure and Analysis of R1 and R2 Pyocin Receptor-Binding Fibers. Viruses 10.
6CP9: Gucinski, G.C., et al. (2019) Convergent Evolution of the Barnase/EndoU/Colicin/RelE (BECR) Fold in Antibacterial tRNase Toxins. Structure 27: 1660.
6CVZ: Loppnau, P., et al. Crystal structure of the WD40-repeat of RFWD3. (TBP)
6D2V: Clinger, J.A., et al. Structure and Function of Terfestatin Biosynthesis Enzymes TerB and TerC. (TBP)
6E4B: Tan, K., et al. The crystal structure of a putative alpha-ribazole-5'-P phosphatase from Escherichia coli str. K-12 substr. MG1655 (CASP target). (TBP)
6EK4: Brauning, B., et al. (2018) Structure and mechanism of the two-component alpha-helical pore-forming toxin YaxAB. Nature Communications 9: 1806-1806.
6F45: Dunne, M., et al. (2018) Salmonella Phage S16 Tail Fiber Adhesin Features a Rare Polyglycine Rich Domain for Host Recognition. Structure 26: 1573-1582.e4.
6M9T: Audet, M., et al. (2019) Crystal structure of misoprostol bound to the labor inducer prostaglandin E2receptor. Nature Chemical Biology 15: 11-17.
6MSP: Koepnick, B., et al. (2019) De novo protein design by citizen scientists. Nature 570: 390-394.
6N64: Birkinshaw, R.W., et al. Structure of SMCHD1 hinge domain. (TBP)
6N9Y: Kerviel, A., et al. (2019) Atomic structure of the translation regulatory protein NS1 of bluetongue virus. Nature Microbiology 4: 837-845.
6ORI: Spiegelman, L., et al. Enterococcal surface protein, partial N-terminal region (CASP target). (TBP)
6PX4: Krieger, I.V., et al. (2020) The Structural Basis of T4 Phage Lysis Control: DNA as the Signal for Lysis Inhibition. Journal of Molecular Biology 432: 4623-4636.
6QVM: Osipov, E.M., et al. Crystal structure of native O-glycosylated multiheme cytochrome cf with S-layer binding domain. (TBP)
6T1Z: Debruycker, V., et al. (2020) An embedded lipid in the multidrug transporter LmrP suggests a mechanism for polyspecificity. Nature Structural & Molecular Biology 27: 829-835.
6TRI: Rasmussen, K.K., et al. (2020) Revealing the mechanism of repressor inactivation during switching of a temperate bacteriophage. PNAS 117: 20576-20585.
6U7L: Minasov, G., et al. 2.75 Angstrom Crystal Structure of Galactarate Dehydratase from Escherichia coli. (TBP)
6UBL: Kosgei, A.J., et al. Structure of DynF from the Dynemicin Biosynthesis Pathway of Micromonospora chersina. (TBP)
6UK5: Alvarado, S.K., et al. Structure of SAM bound CalS10, an amino pentose methyltransferase from Micromonospora echinaspora involved in calicheamicin biosynthesis. (TBP)
6VR4: Leiman, P.G., et al. Virion-packaged DNA-dependent RNA polymerase of crAss-like phage phi14:2 (CASP target). (TBP)
6X6O: Shi, K., et al. (2020) Crystal structure of bacteriophage T4 Spackle as determined by native SAD phasing. Acta Crystallographica Section D 76: 899-904.
6XBD: Coudray, N., et al. Structure of MlaFEDB lipid transporter reveals an ABC exporter fold and two bound phospholipids. (TBP)
6YA2: Bahat, Y., et al. First structure of a glycoprotein from enveloped plant virus. (TBP)
6YFN: Rumnieks, J., et al. Expansion of the structural diversity of single-stranded RNA bacteriophages. (TBP)
6YJ1: Sobieraj, A., et al. (CASP target) Crystal structure of the M23 peptidase domain of Staphylococcal phage 2638A endolysin. (TBP)
7JTL: Flower, T.G., et al. (2020) Structure of SARS-CoV-2 ORF8, a rapidly evolving coronavirus protein implicated in immune evasion. Biorxiv.

[cyberanup]

Request : Please also consider making an 30-40 min version documentary of this with some more details of protein folding and nuances. I have watched AlphaGo documentary over and over again(i'm sure many others would have), and still gives me goosebumps.

[louis-dieudonne]

BREAKING NEWS: This won a Nobel Prize.

[vineetgundecha]

I wish this was longer with all the details!

[sucim]

"The only thing I find more amazing than the rate of progress in AI is the rate in which we get accustomed to it" - Ilya Sutskever

[neousagi]

As a protein chemist and structural biologist, I truly am impressed and congratulations to the DeepMind / Alpha Fold team. This is a major advancement and if you are taking requests, please present a solution structure for apolipoproteins. Their lipid-free state has defied analysis for over 50 years and it would be terrific to have a validated base structure to build upon.

[Cabothedog]

I'm 21 years old, and this is without a doubt one of the biggest scientific advancements in my lifetime

[RedoxAgent]

Absolutely huge... props to developers. Look forward to history in the making.

[Deez-Master]

I have been waiting on the next bombshell from deepmind and boy did they ever deliver!! Being on the life science field myself I can appreciate how absolutely monumental this achievement is

[schneeekind]

4:04 coder starts running... NOW IT'S GETTING SERIOUS 😱😱😱

[HW]

you know we all want a 48min to 1h30 documentary with slow motions, drone shots and epic music

[bxlawless]

I love great scientific achievements. The few people who recognize them in this world applauded your life long efforts!

[nathanlaird]

Indeed, "What will be the next surprise?" is the chief motivator of life. Curiosity and discovery. Excellent work.

[Shapedef]

Congratulations to the Deep Mind team for solving this previously unresolved problem! Fantastic work.

[on-joos]

speaking as someone who was in clinician scientist career, this is a remarkable work which holds the greatest potential for the future. thank you for your work and dedication towards development of human biology and beyond.

[LegionN]

Congratulations and thank you to the DeepMind team for pushing science forward!

[brycemercines]

Congratulations to Deepmind and the Alphafold team, for winning the Nobel Prize!
I hope you create a longer documentary about Alphafold now :)

[TimHuettner]

Please make the background music louder, I can still kind of hear what the people are saying.

[TheAIEpiphany]

04:01 Demis: "We need to double down and go as fast as possible from here"
04:04 Pushmeet: sprinting through the lobby, here I come bossss

Jokes aside <3 love the work you folks at DeepMind are doing.

[pacman]

I haven't a clue what these geeks are talking about but the music sounds like they've are solving a massive problem. Good luck geeks.

[everlearnercaveman]

A paradigm shifting moment in our lifetime. Congratulations to all DeepMind team!