SHAFTS: A Hybrid Approach for 3D Molecular Similarity Calculation. 1. Method and Assessment of Virtual Screening

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• 作者：Xiaofeng Liu ; Hualiang Jiang ; Honglin Li
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2011
• 出版时间：September 26, 2011
• 年：2011
• 卷：51
• 期：9
• 页码：2372-2385
• 全文大小：1106K
• 年卷期：v.51,no.9(September 26, 2011)
• ISSN：1549-960X

文摘

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 鈥渉ybrid similarities鈥? SHAFTS is suitable for large-scale virtual screening with single or multiple bioactive compounds as the query 鈥渢emplates鈥?regardless of whether corresponding experimentally determined conformations are available. Two public test sets (DUD and Jain鈥檚 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.