Community-wide evaluation of methods for predicting the effect of mutations on protein-protein interactions
Authors
Moretti, RoccoFleishman, Sarel J.
Agius, Rudi
Torchala, Mieczyslaw
Bates, Paul A.
Kastritis, Panagiotis L.
Rodrigues, Joao P.G.L.M
Trellet, Mikael
Bonvin, Alexandre M.J.J.
Cui, Meng
Pierce, Brian G.
Hwang, Howook
Vreven, Thom
Weng, Zhiping
Baker, David
UMass Chan Affiliations
Program in Bioinformatics and Integrative BiologyDocument Type
Journal ArticlePublication Date
2013-11-01Keywords
Algorithms*Databases, Protein
Mutation
Protein Binding
*Protein Interaction Mapping
Biochemistry, Biophysics, and Structural Biology
Bioinformatics
Computational Biology
Integrative Biology
Structural Biology
Systems Biology
Metadata
Show full item recordAbstract
Community-wide blind prediction experiments such as CAPRI and CASP provide an objective measure of the current state of predictive methodology. Here we describe a community-wide assessment of methods to predict the effects of mutations on protein-protein interactions. Twenty-two groups predicted the effects of comprehensive saturation mutagenesis for two designed influenza hemagglutinin binders and the results were compared with experimental yeast display enrichment data obtained using deep sequencing. The most successful methods explicitly considered the effects of mutation on monomer stability in addition to binding affinity, carried out explicit side-chain sampling and backbone relaxation, evaluated packing, electrostatic, and solvation effects, and correctly identified around a third of the beneficial mutations. Much room for improvement remains for even the best techniques, and large-scale fitness landscapes should continue to provide an excellent test bed for continued evaluation of both existing and new prediction methodologies.Source
Proteins. 2013 Nov;81(11):1980-7. doi: 10.1002/prot.24356. Epub 2013 Aug 23. Link to article on publisher's siteDOI
10.1002/prot.24356Permanent Link to this Item
http://hdl.handle.net/20.500.14038/25922PubMed ID
23843247Notes
Full author list omitted for brevity. For the full list of authors, see article.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1002/prot.24356
Scopus Count
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