PheSA: An Open-Source Tool for Pharmacophore-Enhanced Shape Alignment.

PheSA is an open-source pharmacophore- and shape-based screening and molecular alignment tool that is fully open-source as part of OpenChemLib. Supporting standard ligand-based screening, flexible refinement of alignments, and receptor-guided shape docking, PheSA is a very flexible tool and can be used for different use cases in structure-based drug design. We present the algorithm and different benchmark studies that investigate the screening performance and also the quality of the generated alignments and the pose prediction performance of the receptor-guided PheSA algorithm. An important finding is the effect of the type of similarity metric used for measuring screening enrichment (symmetric Tanimoto versus asymmetric Tversky), whereby we could observe improved enrichment rates by using Tversky. PheSA exhibits enrichments on the DUD-E that are on par with commercial methods.