Analysis and comparison of 2D fingerprints: Insights into database screening performance using eight fingerprint methods
Analysis and comparison of 2D fingerprints: Insights into database screening performance using eight fingerprint methods
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DOI：
10.1016/j.jmgm.2010.05.008
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发表时间：
2010-09-01
影响因子：
2.9
通讯作者：
Sherman, Woody
中科院分区：
文献类型：
--
作者：
Duan, Jianxin;Dixon, Steven L.;Sherman, Woody
虚拟筛选是现代药物发现中广泛使用的策略，20指纹相似度是已成功应用于从大数据集中检索活性化合物的重要工具。然而，对于给定的问题，选择适当的指纹方法和相关设置并不总是那么简单。在这里，我们应用了八种不同的指纹方法，如在新的化学信息学软件包Canvas中实现的，在一个经过充分验证的数据集上，涵盖了五个目标。指纹图谱方法包括线性、树枝状、径向、MACCS、MOLPRINT2D、成对、三重和扭转。我们发现，大多数指纹有相似的检索率平均，但是，每个有特殊的特点，区分其性能不同的查询分子和配体集。例如，一些指纹表现出显著的配体大小依赖性，而其他指纹相对于查询或活性化合物的变化更稳健。在对活性配体的信息知之甚少的情况下，MOLPRINT2D指纹产生最高的平均检索活性。当有多个查询时，我们发现所有查询分子的平均指纹一般上级来自单个查询的指纹。最后，提出了一个互补性度量，以确定哪些指纹方法可以结合起来，以改善筛选结果。(C)2010年爱思唯尔公司All rights reserved.
Virtual screening is a widely used strategy in modern drug discovery and 20 fingerprint similarity is an important tool that has been successfully applied to retrieve active compounds from large datasets. However, it is not always straightforward to select an appropriate fingerprint method and associated settings for a given problem. Here, we applied eight different fingerprint methods, as implemented in the new cheminformatics package Canvas, on a well-validated dataset covering five targets. The fingerprint methods include Linear, Dendritic, Radial, MACCS, MOLPRINT2D, Pairwise, Triplet, and Torsion. We find that most fingerprints have similar retrieval rates on average; however, each has special characteristics that distinguish its performance on different query molecules and ligand sets. For example, some fingerprints exhibit a significant ligand size dependency whereas others are more robust with respect to variations in the query or active compounds. In cases where little information is known about the active ligands, MOLPRINT2D fingerprints produce the highest average retrieval actives. When multiple queries are available, we find that a fingerprint averaged over all query molecules is generally superior to fingerprints derived from single queries. Finally, a complementarity metric is proposed to determine which fingerprint methods can be combined to improve screening results. (C) 2010 Elsevier Inc. All rights reserved.