SHAFTS (SHApe-FeaTure Similarity) is a program for 3D molecular similarity calculation and ligand-based virtual screening. SHAFTS adopts hybrid similarity metric combined with molecular shape and colored (labeled) chemistry groups annotated by pharmacophore features for 3D similarity calculation and ranking, which is designed to integrated the strength of pharmacophore matching and volumetric overlay approaches. A feature triplet hashing method is used for fast molecular alignment poses enumeration, and the optimal superposition between the target and the query molecules can be prioritized by calculating corresponding “hybrid similarities”. SHAFTS is suitable for large-scale virtual screening with single or multiple bioactive compounds as the query “templates” regardless of whether corresponding experimentally determined conformations are available. Two public test sets (DUD and Jain’s set) including active and decoy molecules from a panel of useful drug targets were adopted to evaluate the virtual screening performance (Liu, et al., Submitted).
SHAFTS performs rigid-body superimposition of 3D molecular models. Single or multiple query structures can be specified. Each target structure is aligned on the individual query structure in turn and the superposition poses corresponding to the highest similarity score is reported. A conformational generation process prior to SHAFTS has to be performed and the all the structures with the same name are regarded as the conformations of the same molecule, and reports the highest similarity score over the set of conformers.
The output file is a regular ASCII text file that can be imported into a spreadsheet program, which containing the names of top N compounds in the order of decreasing hybrid similarity scores. Morever, the superimposed structures for the top N hit molecules are output into a MOL2 file, which can be opened by Pymol or other molecular visualization programs to observe the alignment poses between the query and hit compounds.
- Multiple template molecules as the combined query.
- Flexible post-optimization of the initial superposition poses.
- In Situ calculation of the 3D similarities between the query and sets of superimposed molecules.
SHAFTS is distributed "as is", free of charge, and without warranty of any kind. The use of the program is not restricted, but we appreciate if you acknowledge use of SHAFTS or ChemMapper in any reports or publications of results obtained with SHAFTS and ChemMapper.
- The alias of SHAFTS' execuation is called "Cynthia". A brief description of the available options of SHAFTS are listed when called with the "-h" option.
Cynthia -q query.mol2 -t target.mol2 -o output
Here we superimpose the molecule "target" on the molecule "query", with resulting position of "target" stored in the "outputHits.mol2" and the summary of the similarity score stored in "outputResult.list".
Cynthia -q query.mol2 -t target.mol2 -o output -postOpt
Now the same, but perform post optimiztion to the initial alignment poses.
Cynthia -q query.mol2 -t database.mol2 -o output -n 300 -sCutoff 0.8
Here we screen the molecular database "target.mol2" on the query molecule "query.mol2", with maximum top 300 hit molecules in the order of decreasing hybrid similarity scores stored in the "outputHits.mol2" and the summary of the screening results stored in "outputResult.list". All the molecules with hybrid similarity scores less than 0.8 are discarded.
The "database.mol2" can contain multiple several molecules with single or multiple conformers.