protocol
The FTMap family of web servers for determining and characterizing ligand-binding hot spots of proteins Dima Kozakov1, Laurie E Grove2, David R Hall3, Tanggis Bohnuud1, Scott E Mottarella4, Lingqi Luo4, Bing Xia1, Dmitri Beglov1 & Sandor Vajda1 1Department of
Biomedical Engineering, Boston University, Boston, Massachusetts, USA. 2Department of Sciences, Wentworth Institute of Technology, Boston, Massachusetts, USA. 3Acpharis Inc., Holliston, Massachusetts, USA. 4Program in Bioinformatics, Boston University, Boston, Massachusetts, USA. Correspondence should be addressed to S.V. (
[email protected]) or D.K. (
[email protected]).
© 2015 Nature America, Inc. All rights reserved.
Published online 9 April 2015; doi:10.1038/nprot.2015.043
FTMap is a computational mapping server that identifies binding hot spots of macromolecules—i.e., regions of the surface with major contributions to the ligand-binding free energy. To use FTMap, users submit a protein, DNA or RNA structure in PDB (Protein Data Bank) format. FTMap samples billions of positions of small organic molecules used as probes, and it scores the probe poses using a detailed energy expression. Regions that bind clusters of multiple probe types identify the binding hot spots in good agreement with experimental data. FTMap serves as the basis for other servers, namely FTSite, which is used to predict ligandbinding sites, FTFlex, which is used to account for side chain flexibility, FTMap/param, used to parameterize additional probes and FTDyn, for mapping ensembles of protein structures. Applications include determining the druggability of proteins, identifying ligand moieties that are most important for binding, finding the most bound-like conformation in ensembles of unliganded protein structures and providing input for fragment-based drug design. FTMap is more accurate than classical mapping methods such as GRID and MCSS, and it is much faster than the more-recent approaches to protein mapping based on mixed molecular dynamics. By using 16 probe molecules, the FTMap server finds the hot spots of an average-size protein in
