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Prediction of protein–protein binding free energies
Author(s) -
Vreven Thom,
Hwang Howook,
Pierce Brian G.,
Weng Zhiping
Publication year - 2012
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.2027
Subject(s) - protein function , benchmark (surveying) , residue (chemistry) , function (biology) , chemistry , protein structure , biological system , statistical physics , physics , thermodynamics , biochemistry , biology , geodesy , evolutionary biology , gene , geography
We present an energy function for predicting binding free energies of protein–protein complexes, using the three‐dimensional structures of the complex and unbound proteins as input. Our function is a linear combination of nine terms and achieves a correlation coefficient of 0.63 with experimental measurements when tested on a benchmark of 144 complexes using leave‐one‐out cross validation. Although we systematically tested both atomic and residue‐based scoring functions, the selected function is dominated by residue‐based terms. Our function is stable for subsets of the benchmark stratified by experimental pH and extent of conformational change upon complex formation, with correlation coefficients ranging from 0.61 to 0.66.