TY - JOUR
T1 - Community-wide evaluation of methods for predicting the effect of mutations on protein-protein interactions
AU - Moretti, Rocco
AU - Fleishman, Sarel J.
AU - Agius, Rudi
AU - Torchala, Mieczyslaw
AU - Bates, Paul A.
AU - Kastritis, Panagiotis L.
AU - Rodrigues, Joao P. G. L. M.
AU - Trellet, Mikael
AU - Bonvin, Alexandre M. J. J.
AU - Cui, Meng
AU - Rooman, Marianne
AU - Gillis, Dimitri
AU - Dehouck, Yves
AU - Moal, Iain
AU - Romero-Durana, Miguel
AU - Perez-Cano, Laura
AU - Pallara, Chiara
AU - Jimenez, Brian
AU - Fernandez-Recio, Juan
N1 - National Science Foundation [DBI-0845196, IOS-1126992]; Spanish Ministry of Science [BIO2010-22324]; Defense Threat Reduction Agency [HDTRA1-10-0040]Grant sponsor: National Science Foundation; grant number: DBI-0845196 to D. K; Grant sponsor: National Science Foundation; grant number: IOS-1126992 to N.Z.; Grant sponsor: Spanish Ministry of Science; grant number: BIO2010-22324 to J. F.-R; Grant sponsor: Defense Threat Reduction Agency; grant number: HDTRA1-10-0040 to D.B..
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84885836021&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/prot.24356
DO - https://doi.org/10.1002/prot.24356
M3 - مقالة
SN - 0887-3585
VL - 81
SP - 1980
EP - 1987
JO - Proteins-Structure Function And Bioinformatics
JF - Proteins-Structure Function And Bioinformatics
IS - 11
ER -