Rapid Comparison of Protein Binding Sites
Comparing protein binding sites is an important method in drug discovery that plays a part in a wide variety of structure-centric pursuits. One challenge for binding site comparison methods is the broad goals of such approaches: from identifying subtle differences between largely similar sites in induced fit analysis or understanding selectivity, to identifying general similarity for drug repurposing or target fishing searches.
SiteHopper represents an application of the OpenEye Shape and Color approach that has been so successful in ROCS to the domain of protein comparison. Treating binding sites as constructs with a defined shape and set of chemical features allows for rapid searching of database of known structures Users can generate their own protein database to search or use our provided database of publicly available structures. Users can then compare a query protein to a database of hundreds of thousands of protein binding sites in just a few minutes on an Nvidia GPU. The speed and flexibility of SiteHopper opens new avenues in drug repurposing, predicting off target effects, and polypharmacology among other uses in drug design projects.
Prediction of Protein Pairs Sharing Common Active Ligands Using Protein Sequence, Structure, and Ligand Similarity. Yu-Chen Chen, Robert Tolbert, Alex M. Aronov, Georgia McGaughey, W. Patrick Walters, and Lidio Meirele. Journal of Chemical Information and Modeling 2016 56 (9), 1734-1745. DOI: 10.1021/acs.jcim.6b00118
Privileged Structures and Polypharmacology within and between Protein Families. Joshua Meyers, Nicola E. A. Chessum, Salyha Ali, N. Yi Mok, Birgit Wilding, A. Elisa Pasqua, Martin Rowlands, Michael J. Tucker, Lindsay E. Evans, Carl S. Rye, Lisa O’Fee, Yann-Vaï Le Bihan, Rosemary Burke, Michael Carter, Paul Workman, Julian Blagg, Nathan Brown, Rob L. M. van Montfort, Keith Jones, and Matthew D. Cheeseman. ACS Medicinal Chemistry Letters 2018 9 (12), 1199-1204. DOI: 10.1021/acsmedchemlett.8b00364