Prediction of protein-protein binding free energies

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Program in Bioinformatics and Integrative Biology



Document Type


Medical Subject Headings

Algorithms; Antigen-Antibody Complex; Entropy; *Protein Binding; Protein Conformation; Proteins; Thermodynamics


Biochemistry, Biophysics, and Structural Biology | Bioinformatics | Computational Biology | Systems Biology


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.

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Citation: Protein Sci. 2012 Mar;21(3):396-404. doi: 10.1002/pro.2027. Epub 2012 Feb 2. Link to article on publisher's site

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