title: SHAFTS: a hybrid approach for 3D molecular similarity calculation. 1. Method and assessment of virtual screening.
abstract: We developed a novel approach called SHAFTS (SHApe-FeaTure Similarity) for 3D molecular similarity calculation and ligand-based virtual screening. SHAFTS adopts a 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 integrate 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 sets) including active and decoy molecules from a panel of useful drug targets were adopted to evaluate the virtual screening performance. SHAFTS outperformed several other widely used virtual screening methods in terms of enrichment of known active compounds as well as novel chemotypes, thereby indicating its robustness in hit compounds identification and potential of scaffold hopping in virtual screening.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Liu
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Honglin
authors.initials: H
authors.lastname: Li
mesh_terms: D004353:Drug Evaluation, Preclinical; D008958:Models, Molecular; D015394:Molecular Structure