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.
Chem Biol Drug Des. 2010 Sep 1;76(3):191-200. doi: 10.1111/j.1747-0285.2010.01007.x. Epub 2010 Jul 15.
Ligand- and target structure-based methods are widely used in virtual screening, but there is currently no methodology available that fully integrates these different approaches. Herein, we provide an overview of various attempts that have been made to combine ligand- and structure-based computational screening methods. We then review different types of approaches that utilize protein-ligand interaction information for database screening and filtering. Interaction-based approaches make use of a variety of methodological concepts including pharmacophore modeling and direct or indirect encoding of protein-ligand interactions in fingerprint formats. These interaction-based methods have been successfully applied to tackle different tasks related to virtual screening including postprocessing of docking poses, prioritization of binding modes, selectivity analysis, or similarity searching. Furthermore, we discuss the recently developed interacting fragment approach that indirectly incorporates 3D interaction information into 2D similarity searching and bridges between ligand- and structure-based methods.
配体和基于靶标的方法广泛应用于虚拟筛选，但目前尚无完全整合这些不同方法的方法学。本文综述了将配体和基于结构的计算筛选方法相结合的各种尝试。然后，我们回顾了利用蛋白质-配体相互作用信息进行数据库筛选和过滤的不同类型的方法。基于相互作用的方法利用了各种方法学概念，包括药效团建模以及直接或间接以指纹格式编码蛋白质-配体相互作用。这些基于相互作用的方法已成功应用于解决与虚拟筛选相关的不同任务，包括对接构象的后处理、结合模式的优先级排序、选择性分析或相似性搜索。此外，我们还讨论了最近开发的交互片段方法，该方法将 3D 相互作用信息间接纳入 2D 相似性搜索中，并在配体和基于结构的方法之间架起了桥梁。
