A Thoroughly Validated Virtual Screening Strategy for Discovery of Novel HDAC3 Inhibitors
AbstractHistone deacetylase 3 (HDAC3) has been recently identified as a potential target for the treatment of cancer and other diseases, such as chronic inflammation, neurodegenerative diseases, and diabetes. Virtual screening (VS) is currently a routine technique for hit identification, but its success depends on rational development of VS strategies. To facilitate this process, we applied our previously released benchmarking dataset, i.e., MUBD-HDAC3 to the evaluation of structure-based VS (SBVS) and ligand-based VS (LBVS) combinatorial approaches. We have identified FRED (Chemgauss4) docking against a structural model of HDAC3, i.e., SAHA-3 generated by a computationally inexpensive “flexible docking”, as the best SBVS approach and a common feature pharmacophore model, i.e., Hypo1 generated by Catalyst/HipHop as the optimal model for LBVS. We then developed a pipeline that was composed of Hypo1, FRED (Chemgauss4), and SAHA-3 sequentially, and demonstrated that it was superior to other combinations in terms of ligand enrichment. In summary, we present the first highly-validated, rationally-designed VS strategy specific to HDAC3 inhibitor discovery. The constructed pipeline is publicly accessible for the scientific community to identify novel HDAC3 inhibitors in a time-efficient and cost-effective way. View Full-Text
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Hu, H.; Xia, J.; Wang, D.; Wang, X.S.; Wu, S. A Thoroughly Validated Virtual Screening Strategy for Discovery of Novel HDAC3 Inhibitors. Int. J. Mol. Sci. 2017, 18, 137.
Hu H, Xia J, Wang D, Wang XS, Wu S. A Thoroughly Validated Virtual Screening Strategy for Discovery of Novel HDAC3 Inhibitors. International Journal of Molecular Sciences. 2017; 18(1):137.Chicago/Turabian Style
Hu, Huabin; Xia, Jie; Wang, Dongmei; Wang, Xiang S.; Wu, Song. 2017. "A Thoroughly Validated Virtual Screening Strategy for Discovery of Novel HDAC3 Inhibitors." Int. J. Mol. Sci. 18, no. 1: 137.
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