AlphaFold: hoe een wetenschappelijke doorbraak tot stand kwam AlphaFold: The making of a scientific breakthrough

Het verhaal van binnenuit over het team van wetenschappers en engineers van DeepMind dat AlphaFold maakte, een AI-systeem dat wordt erkend als oplossing voor "eiwitvouwing", al meer dan 50 jaar een grote wetenschappelijke uitdaging. Meer weten: deepmind.com/alphafold Eiwitreferenties: TBP = To be published (nog te publiceren) 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.

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. Find out more: deepmind.com/alphafold 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.