Back to Search
Start Over
Community-Wide Assessment of Protein-Interface Modeling Suggests Improvements to Design Methodology
- Source :
- Journal of Molecular Biology, Journal of Molecular Biology, Elsevier, 2011, 414 (2), in press. ⟨10.1016/j.jmb.2011.09.031⟩, Journal of Molecular Biology, Elsevier, 2011, in press. ⟨10.1016/j.jmb.2011.09.031⟩, Journal of Molecular Biology, 2011, 414 (2), in press. ⟨10.1016/j.jmb.2011.09.031⟩, Journal of Molecular Biology, 414(2), 289. Academic Press Inc.
- Publication Year :
- 2011
- Publisher :
- HAL CCSD, 2011.
-
Abstract
- International audience; The CAPRI (Critical Assessment of Predicted Interactions) and CASP (Critical Assessment of protein Structure Prediction) experiments have demonstrated the power of community-wide tests of methodology in assessing the current state of the art and spurring progress in the very challenging areas of protein docking and structure prediction. We sought to bring the power of community-wide experiments to bear on a very challenging protein design problem that provides a complementary but equally fundamental test of current understanding of protein-binding thermodynamics. We have generated a number of designed protein-protein interfaces with very favorable computed binding energies but which do not appear to be formed in experiments, suggesting that there may be important physical chemistry missing in the energy calculations. A total of 28 research groups took up the challenge of determining what is missing: we provided structures of 87 designed complexes and 120 naturally occurring complexes and asked participants to identify energetic contributions and/or structural features that distinguish between the two sets. The community found that electrostatics and solvation terms partially distinguish the designs from the natural complexes, largely due to the nonpolar character of the designed interactions. Beyond this polarity difference, the community found that the designed binding surfaces were, on average, structurally less embedded in the designed monomers, suggesting that backbone conformational rigidity at the designed surface is important for realization of the designed function. These results can be used to improve computational design strategies, but there is still much to be learned; for example, one designed complex, which does form in experiments, was classified by all metrics as a nonbinder.
- Subjects :
- Models, Molecular
biochemistry and molecular biology
Computer science
Protein design
Nanotechnology
Machine learning
computer.software_genre
Article
03 medical and health sciences
Structural Biology
protein protein interactions
Taverne
conformational plasticity
Computational design
Macromolecular docking
CASP
Design methods
Molecular Biology
030304 developmental biology
Protein interface
0303 health sciences
Binding Sites
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]
business.industry
030302 biochemistry & molecular biology
Proteins
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
negative design
Docking (molecular)
computational protein design
Critical assessment
Artificial intelligence
business
computer
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 00222836 and 10898638
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular Biology, Journal of Molecular Biology, Elsevier, 2011, 414 (2), in press. ⟨10.1016/j.jmb.2011.09.031⟩, Journal of Molecular Biology, Elsevier, 2011, in press. ⟨10.1016/j.jmb.2011.09.031⟩, Journal of Molecular Biology, 2011, 414 (2), in press. ⟨10.1016/j.jmb.2011.09.031⟩, Journal of Molecular Biology, 414(2), 289. Academic Press Inc.
- Accession number :
- edsair.doi.dedup.....abc9fe98b9e40ef44a6829a3e83984a1