A structural biology community assessment of AlphaFold2 applications
Por:
Akdel, M, Pires, DEV, Pardo, EP, Janes, J, Zalevsky, AO, Meszaros, B, Bryant, P, Good, LL, Laskowski, RA, Pozzati, G, Shenoy, A, Zhu, WS, Kundrotas, P, Serra, VR, Rodrigues, CHM, Dunham, AS, Burke, D, Borkakoti, N, Velankar, S, Frost, A, Basquin, J, Lindorff-Larsen, K, Bateman, A, Kajava, AV, Valencia, A, Ovchinnikov, S, Durairaj, J, Ascher, DB, Thornton, JM, Davey, NE, Stein, A, Elofsson, A, Croll, TI and Beltrao, P
Publicada:
1 nov 2022
Ahead of Print:
1 nov 2022
Resumen:
Here, the authors evaluate the performance of AlphaFold2 and its predicted structures on common structural biological applications, including missense variants, function and ligand binding site prediction, modeling of interactions and modeling of experimental structural data.
Most proteins fold into 3D structures that determine how they function and orchestrate the biological processes of the cell. Recent developments in computational methods for protein structure predictions have reached the accuracy of experimentally determined models. Although this has been independently verified, the implementation of these methods across structural-biology applications remains to be tested. Here, we evaluate the use of AlphaFold2 (AF2) predictions in the study of characteristic structural elements; the impact of missense variants; function and ligand binding site predictions; modeling of interactions; and modeling of experimental structural data. For 11 proteomes, an average of 25% additional residues can be confidently modeled when compared with homology modeling, identifying structural features rarely seen in the Protein Data Bank. AF2-based predictions of protein disorder and complexes surpass dedicated tools, and AF2 models can be used across diverse applications equally well compared with experimentally determined structures, when the confidence metrics are critically considered. In summary, we find that these advances are likely to have a transformative impact in structural biology and broader life-science research.
Filiaciones:
Akdel, M:
Wageningen Univ & Res, Bioinformat Grp, Dept Plant Sci, Wageningen, Netherlands
Pires, DEV:
Univ Melbourne, Sch Comp and Informat Syst, Melbourne, Vic, Australia
:
Josep Carreras Leukaemia Res Inst IJC, Badalona, Spain
Barcelona Supercomp Ctr BSC, Barcelona, Spain
Janes, J:
European Bioinformat Inst, European Mol Biol Lab, Cambridge, England
Zalevsky, AO:
Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia
Meszaros, B:
European Mol Biol Lab, Heidelberg, Germany
Bryant, P:
Dept Biochem & Biophys, Solna, Sweden
Sci Life Lab, Solna, Sweden
Good, LL:
Univ Copenhagen, Dept Biol, Linderstrom Lang Ctr Prot Sci, Copenhagen, Denmark
Laskowski, RA:
European Bioinformat Inst, European Mol Biol Lab, Cambridge, England
Pozzati, G:
Dept Biochem & Biophys, Solna, Sweden
Sci Life Lab, Solna, Sweden
Shenoy, A:
Dept Biochem & Biophys, Solna, Sweden
Sci Life Lab, Solna, Sweden
Zhu, WS:
Dept Biochem & Biophys, Solna, Sweden
Sci Life Lab, Solna, Sweden
Kundrotas, P:
Dept Biochem & Biophys, Solna, Sweden
Sci Life Lab, Solna, Sweden
Serra, VR:
Barcelona Supercomp Ctr BSC, Barcelona, Spain
Rodrigues, CHM:
Univ Melbourne, Sch Comp and Informat Syst, Melbourne, Vic, Australia
Dunham, AS:
European Bioinformat Inst, European Mol Biol Lab, Cambridge, England
Burke, D:
European Bioinformat Inst, European Mol Biol Lab, Cambridge, England
Borkakoti, N:
European Bioinformat Inst, European Mol Biol Lab, Cambridge, England
Velankar, S:
European Bioinformat Inst, European Mol Biol Lab, Cambridge, England
Frost, A:
Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA
Basquin, J:
Max Planck Inst Biochem, Dept Struct Cell Biol, Martinsried, Germany
Lindorff-Larsen, K:
Univ Copenhagen, Dept Biol, Linderstrom Lang Ctr Prot Sci, Copenhagen, Denmark
Bateman, A:
European Bioinformat Inst, European Mol Biol Lab, Cambridge, England
Kajava, AV:
Univ Montpellier, Ctr Rech Biol Cellulaire Montpellier, Montpellier, France
Valencia, A:
Barcelona Supercomp Ctr BSC, Barcelona, Spain
Ovchinnikov, S:
Harvard Univ, Div Sci, Fac Arts & Sci, Cambridge, MA 02138 USA
Durairaj, J:
Univ Basel, Biozentrum, Basel, Switzerland
Ascher, DB:
Univ Queensland, Sch Chem and Sci, Div Sci, Brisbane, Qld, Australia
Thornton, JM:
European Bioinformat Inst, European Mol Biol Lab, Cambridge, England
Davey, NE:
Inst Canc Res, London, England
Stein, A:
Univ Copenhagen, Dept Biol, Linderstrom Lang Ctr Prot Sci, Copenhagen, Denmark
Elofsson, A:
Dept Biochem & Biophys, Solna, Sweden
Sci Life Lab, Solna, Sweden
Croll, TI:
Univ Cambridge, Dept Haematol, Cambridge Inst Med Res, Cambridge, England
Beltrao, P:
European Bioinformat Inst, European Mol Biol Lab, Cambridge, England
Swiss Fed Inst Technol, Inst Mol Syst Biol, Zurich, Switzerland
Green Submitted, Green Published, hybrid
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