Document Type
Peer-Reviewed Article
Publication Date
2-2009
Abstract
In a previous paper, we described a novel empirical free energy function that was used to accurately predict experimental binding free energies for a diverse test set of 31 protein–protein complexes to within ≈1.0 kcal. Here, we extend that work and show that an updated version of the function can be used to (1) accurately predict native binding free energies and (2) rank crystallographic, native-like and non-native binding modes in a physically realistic manner. The modified function includes terms designed to capture some of the unfavorable interactions that characterize non-native interfaces. The function was used to calculate one-dimensional binding free energy surfaces for 21 protein complexes. In roughly 90% of the cases tested, the function was used to place native-like and crystallographic binding modes in global free energy minima. Our analysis further suggests that buried hydrogen bonds might provide the key to distinguishing native from non-native interactions. To the best of our knowledge our function is the only one of its kind, a single expression that can be used to accurately calculate native and non-native binding free energies for a large number of proteins. Given the encouraging results presented in this paper, future work will focus on improving the function and applying it to the protein–protein docking problem
DOI
10.1016/j.bpc.2008.10.007
PubMed ID
19041170
Recommended Citation
Audie, J. (2009). Development and validation of an empirical free energy function for calculating protein–protein binding free energy surfaces. Biophysical Chemistry,139(2/3), 84-91. Doi: 10.1016/j.bpc.2008.10.007
