Identification of direct residue contacts in protein-protein interaction by message passing.
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TLDR
This work has developed a method that combines covariance analysis with global inference analysis and successfully and robustly identified residue pairs that are proximal in space without resorting to ad hoc tuning parameters, both for heterointeractions between sensor kinase and response regulator proteins and for homointer interactions between RR proteins.Abstract:
Understanding the molecular determinants of specificity in protein–protein interaction is an outstanding challenge of postgenome biology. The availability of large protein databases generated from sequences of hundreds of bacterial genomes enables various statistical approaches to this problem. In this context covariance-based methods have been used to identify correlation between amino acid positions in interacting proteins. However, these methods have an important shortcoming, in that they cannot distinguish between directly and indirectly correlated residues. We developed a method that combines covariance analysis with global inference analysis, adopted from use in statistical physics. Applied to a set of >2,500 representatives of the bacterial two-component signal transduction system, the combination of covariance with global inference successfully and robustly identified residue pairs that are proximal in space without resorting to ad hoc tuning parameters, both for heterointeractions between sensor kinase (SK) and response regulator (RR) proteins and for homointeractions between RR proteins. The spectacular success of this approach illustrates the effectiveness of the global inference approach in identifying direct interaction based on sequence information alone. We expect this method to be applicable soon to interaction surfaces between proteins present in only 1 copy per genome as the number of sequenced genomes continues to expand. Use of this method could significantly increase the potential targets for therapeutic intervention, shed light on the mechanism of protein–protein interaction, and establish the foundation for the accurate prediction of interacting protein partners.read more
Citations
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Highly accurate protein structure prediction with AlphaFold
John M. Jumper,Richard O. Evans,Alexander Pritzel,Tim Green,Michael Figurnov,Olaf Ronneberger,Kathryn Tunyasuvunakool,Russell Bates,Augustin Žídek,Anna Potapenko,Alex Bridgland,Clemens Meyer,Simon A. A. Kohl,Andrew J. Ballard,Andrew Cowie,Bernardino Romera-Paredes,Stanislav Nikolov,R. D. Jain,Jonas Adler,Trevor Back,Stig Petersen,David Reiman,Ellen Clancy,Michal Zielinski,Martin Steinegger,Michalina Pacholska,Tamas Berghammer,Sebastian Bodenstein,David L. Silver,Oriol Vinyals,Andrew W. Senior,Koray Kavukcuoglu,Pushmeet Kohli,Demis Hassabis +33 more
TL;DR: For example, AlphaFold as mentioned in this paper predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture. But the accuracy is limited by the fact that no homologous structure is available.
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Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: a historical perspective.
TL;DR: The availability of structural information has significantly increased for many organisms as a direct consequence of the complementary nature of comparative protein modeling and experimental structure determination, which has a very positive and enabling impact on many different applications in biomedical research.
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Opportunities and obstacles for deep learning in biology and medicine.
Travers Ching,Daniel Himmelstein,Brett K. Beaulieu-Jones,Alexandr A. Kalinin,Brian T. Do,Gregory P. Way,Enrico Ferrero,Paul-Michael Agapow,Michael Zietz,Michael M. Hoffman,Michael M. Hoffman,Wei Xie,Gail L. Rosen,Benjamin J. Lengerich,Johnny Israeli,Jack Lanchantin,Stephen Woloszynek,Anne E. Carpenter,Avanti Shrikumar,Jinbo Xu,Evan M. Cofer,Evan M. Cofer,Christopher A. Lavender,Srinivas C. Turaga,Amr Alexandari,Zhiyong Lu,David J. Harris,Dave DeCaprio,Yanjun Qi,Anshul Kundaje,Yifan Peng,Laura K. Wiley,Marwin H. S. Segler,Simina M. Boca,S. Joshua Swamidass,Austin Huang,Anthony Gitter,Anthony Gitter,Casey S. Greene +38 more
TL;DR: It is found that deep learning has yet to revolutionize biomedicine or definitively resolve any of the most pressing challenges in the field, but promising advances have been made on the prior state of the art.
Journal ArticleDOI
Direct-coupling analysis of residue coevolution captures native contacts across many protein families
Faruck Morcos,Andrea Pagnani,Bryan Lunt,Arianna Bertolino,Debora S. Marks,Chris Sander,Riccardo Zecchina,José N. Onuchic,Terence Hwa,Martin Weigt +9 more
TL;DR: The findings suggest that contacts predicted by DCA can be used as a reliable guide to facilitate computational predictions of alternative protein conformations, protein complex formation, and even the de novo prediction of protein domain structures, contingent on the existence of a large number of homologous sequences which are being rapidly made available due to advances in genome sequencing.
Journal ArticleDOI
Protein 3D structure computed from evolutionary sequence variation.
Debora S. Marks,Lucy J. Colwell,Robert L. Sheridan,Thomas A. Hopf,Andrea Pagnani,Riccardo Zecchina,Chris Sander +6 more
TL;DR: Surprisingly, it is found that the strength of these inferred couplings is an excellent predictor of residue-residue proximity in folded structures, and the top-scoring residue couplings are sufficiently accurate and well-distributed to define the 3D protein fold with remarkable accuracy.
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