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- Title
Enrichment Assessment of Multiple Virtual Screening Strategies for Toll-Like Receptor 8 Agonists Based on a Maximal Unbiased Benchmarking Data Set.
- Authors
Pei, Fen; Jin, Hongwei; Zhou, Xin; Xia, Jie; Sun, Lidan; Liu, Zhenming; Zhang, Liangren
- Abstract
Toll-like receptor 8 agonists, which activate adaptive immune responses by inducing robust production of T-helper 1-polarizing cytokines, are promising candidates for vaccine adjuvants. As the binding site of toll-like receptor 8 is large and highly flexible, virtual screening by individual method has inevitable limitations; thus, a comprehensive comparison of different methods may provide insights into seeking effective strategy for the discovery of novel toll-like receptor 8 agonists. In this study, the performance of knowledge-based pharmacophore, shape-based 3D screening, and combined strategies was assessed against a maximum unbiased benchmarking data set containing 13 actives and 1302 decoys specialized for toll-like receptor 8 agonists. Prior structure-activity relationship knowledge was involved in knowledge-based pharmacophore generation, and a set of antagonists was innovatively used to verify the selectivity of the selected knowledge-based pharmacophore. The benchmarking data set was generated from our recently developed ' mubd-decoymaker' protocol. The enrichment assessment demonstrated a considerable performance through our selected three-layer virtual screening strategy: knowledge-based pharmacophore ( Phar1) screening, shape-based 3D similarity search ( Q4_combo), and then a Gold docking screening. This virtual screening strategy could be further employed to perform large-scale database screening and to discover novel toll-like receptor 8 agonists.
- Subjects
TOLL-like receptors; IMMUNE response; CYTOKINES; BINDING sites; STRUCTURE-activity relationship in pharmacology; MOLECULAR docking
- Publication
Chemical Biology & Drug Design, 2015, Vol 86, Issue 5, p1226
- ISSN
1747-0277
- Publication type
Article
- DOI
10.1111/cbdd.12590