Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstr. 2, D-53113 Bonn, Germany.
Future Med Chem. 2012 Apr;4(5):603-13. doi: 10.4155/fmc.12.18.
Structure-based virtual screening makes explicit or implicit use of 3D target structure information to detect novel active compounds. Results of nearly 300 currently available original applications have been analyzed to characterize the state-of-the-art in this field. Compound selection from docking calculations is much influenced by subjective criteria. Although submicromolar compounds are identified, the majority of docking hits are only weakly potent. However, only a small percentage of docking hits can be reproduced by ligand-based methods. When docking calculations identify potent hits, they often originate from specialized compound sources (e.g., pharmaceutical compound decks or target-focused libraries) and also display a notable bias towards kinase targets. Structure-based virtual screening is the dominant approach to computational hit identification. Docking calculations frequently identify active compounds. Limited accuracy of compound scoring and ranking currently presents a major caveat of the approach that is often compensated for by chemical intuition and knowledge.
基于结构的虚拟筛选明确或隐含地使用 3D 目标结构信息来检测新型活性化合物。分析了近 300 项现有原始应用的结果，以描述该领域的最新技术状态。从对接计算中选择化合物受到主观标准的极大影响。尽管鉴定出了亚毫摩尔化合物，但大多数对接命中仅具有微弱的效力。然而，只有一小部分对接命中可以通过基于配体的方法重现。当对接计算确定有效的命中时，它们通常来自专门的化合物来源（例如，制药化合物库或针对目标的文库），并且也明显偏向于激酶靶标。基于结构的虚拟筛选是计算命中识别的主要方法。对接计算经常识别出活性化合物。化合物评分和排序的准确性有限，目前是该方法的一个主要缺点，通常通过化学直觉和知识来弥补。
