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Predicting Binding Free Energy Change Caused by Point Mutations with Knowledge-Modified MM/PBSA Method.

Authors :
Petukh, Marharyta
Li, Minghui
Alexov, Emil
Source :
PLoS Computational Biology; 7/6/2015, Vol. 11 Issue 7, p1-23, 23p, 8 Charts, 6 Graphs
Publication Year :
2015

Abstract

A new methodology termed Single Amino Acid Mutation based change in Binding free Energy (SAAMBE) was developed to predict the changes of the binding free energy caused by mutations. The method utilizes 3D structures of the corresponding protein-protein complexes and takes advantage of both approaches: sequence- and structure-based methods. The method has two components: a MM/PBSA-based component, and an additional set of statistical terms delivered from statistical investigation of physico-chemical properties of protein complexes. While the approach is rigid body approach and does not explicitly consider plausible conformational changes caused by the binding, the effect of conformational changes, including changes away from binding interface, on electrostatics are mimicked with amino acid specific dielectric constants. This provides significant improvement of SAAMBE predictions as indicated by better match against experimentally determined binding free energy changes over 1300 mutations in 43 proteins. The final benchmarking resulted in a very good agreement with experimental data (correlation coefficient 0.624) while the algorithm being fast enough to allow for large-scale calculations (the average time is less than a minute per mutation). [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1553734X
Volume :
11
Issue :
7
Database :
Complementary Index
Journal :
PLoS Computational Biology
Publication Type :
Academic Journal
Accession number :
108628980
Full Text :
https://doi.org/10.1371/journal.pcbi.1004276