AlloPred: prediction of allosteric pockets on proteins using normal mode perturbation analysis.
BACKGROUND
Despite being hugely important in biological processes, allostery is poorly understood and no universal mechanism has been discovered. Allosteric drugs are a largely unexplored prospect with many potential advantages over orthosteric drugs. Computational methods to predict allosteric sites on proteins are needed to aid the discovery of allosteric drugs, as well as to advance our fundamental understanding of allostery.


RESULTS
AlloPred, a novel method to predict allosteric pockets on proteins, was developed. AlloPred uses perturbation of normal modes alongside pocket descriptors in a machine learning approach that ranks the pockets on a protein. AlloPred ranked an allosteric pocket top for 23 out of 40 known allosteric proteins, showing comparable and complementary performance to two existing methods. In 28 of 40 cases an allosteric pocket was ranked first or second. The AlloPred web server, freely available at http://www.sbg.bio.ic.ac.uk/allopred/home, allows visualisation and analysis of predictions. The source code and dataset information are also available from this site.


CONCLUSIONS
Perturbation of normal modes can enhance our ability to predict allosteric sites on proteins. Computational methods such as AlloPred assist drug discovery efforts by suggesting sites on proteins for further experimental study.
Centre for Integrative Systems Biology and Bioinformatics, Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK. joe.greener13@imperial.ac.uk.
Joe G
JG
Greener
Centre for Integrative Systems Biology and Bioinformatics, Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
Michael J E
MJ
Sternberg
D000465:Algorithms; D000495:Allosteric Site; D008024:Ligands; D011487:Protein Conformation; D011506:Proteins / Q000378:metabolism*
D008024:Ligands; D011506:Proteins