文献类型：期刊文献

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

作者：Liu, Xiaofeng[1,2];Jiang, Hualiang[2];Li, Honglin[1]

机构：[1]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China

年份：2011

卷号：51

期号：9

起止页码：2372

外文期刊名：JOURNAL OF CHEMICAL INFORMATION AND MODELING

收录：;EI(收录号：20114014395139);WOS:【SCI-EXPANDED(收录号:WOS:000295114700033)】；

基金：This work was supported by the Fundamental Research Funds for the Central Universities, the National Natural Science Foundation of China (grants 20803022, 21173076, and 81102375), the Special Fund for Major State Basic Research Project (grants 2009CB918501 and 2011CB910200), the Shanghai Committee of Science and Technology (grants 09dZ1975700 and 10431902600), and the National S&T Major Project of China (grant 2011ZX09307-002-03). Honglin Li is also sponsored by Shanghai Rising-Star Program (grant 10QA1401800) and Program for New Century Excellent Talents in University (grant NCET-10-0378). The authors thank Open-Eye Scientific Software Inc. and Accelrys Inc. We are also grateful to Dr. Mikko J. Vainio for making the programs ShaEP and Balloon publicly available.

语种：英文

外文关键词：Scaffolds - Pharmacodynamics - Calculations

摘要：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.