SHAFTS: A Hybrid Approach for 3D Molecular Similarity Calculation. 1. Method and Assessment of Virtual Screening
SHAFTS: A Hybrid Approach for 3D Molecular Similarity Calculation. 1. Method and Assessment of Virtual Screening
复制标题
轴：3D 分子相似性计算的混合方法。
DOI：
10.1021/ci200060s
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发表时间：
2011-09-01
影响因子：
5.6
通讯作者：
Li, Honglin
中科院分区：
文献类型：
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作者：
Liu, Xiaofeng;Jiang, Hualiang;Li, Honglin
我们开发了一种新的方法，称为SHIFTS(形状-特征相似性)，用于三维分子相似性计算和基于配体的虚拟筛选。SHIFTS采用混合相似性度量，结合分子形状和由药效团特征标注的有色(标记)化学基团进行3D相似性计算和排序，旨在整合药效团匹配和体积覆盖方法的优势。使用特征三元组散列法进行快速分子比对姿态枚举，通过计算相应的杂交相似度来确定目标分子和查询分子之间的最优叠加的优先顺序。无论是否有相应的实验确定的构象可用，SHIFTS都适用于以单个或多个生物活性化合物作为查询“模板”的大规模虚拟筛选。两个公共测试集(DUD和Jain的集)被用来评估虚拟筛选性能，这些测试集包括来自一组有用的药物目标的活性分子和诱饵分子。在已知活性化合物和新的化学类型的丰富方面，SHIFTS的表现优于其他几种广泛使用的虚拟筛选方法，从而表明它在命中化合物鉴定中的稳健性和在虚拟筛选中支架跳跃的潜力。
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.