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Proteins. 2013 Nov;81(11):1980-7. doi: 10.1002/prot.24356. Epub 2013 Aug 23.

Community-wide evaluation of methods for predicting the effect of mutations on protein-protein interactions.

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  • 1Department of Biochemistry, University of Washington, Seattle, Washington, 98195.

Abstract

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.

© 2013 Wiley Periodicals, Inc.

KEYWORDS:

CAPRI; binding; deep mutational scanning; hemagglutinin; yeast display

PMID:
23843247
[PubMed - indexed for MEDLINE]
PMCID:
PMC4143140
Free PMC Article
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