Refined pharmacophore features for virtual screening of human thromboxane A2 receptor antagonists.

Baichun Hu, Johnson Joseph, Xiaohui Geng, Yiheng Wu, Muhammad R Suleiman, Xinyue Liu, Jiyue Shi, Xiujun Wang, Zhicheng He, Jian Wang, Maosheng Cheng

Computational biology and chemistry 2020 Jun

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For a long time, the structural basis of TXA2 receptor is limited due to the lack of crystal structure information, till the release of the crystal structure of TXA2 receptor, which deepens our understanding about ligand recognition and selectivity mechanisms of this physiologically important receptor. In this research, we report the successful implementation in the discovery of an optimal pharmacophore model of human TXA2 receptor antagonists through virtual screening. Structure-based pharmacophore models were generated based on two crystal structures of human TXA2 receptor (PDB entry 6IIU and 6IIV). Docking simulation revealed interaction modes of the virtual screening hits against TXA2 receptor, which was validated through molecular dynamics simulation and binding free energy calculation. ADMET properties were also analyzed to evaluate the toxicity and physio-chemical characteristics of the hits. The research would provide valuable insight into the binding mechanisms of TXA2 receptor antagonists and thus be helpful for designing novel antagonists. Copyright © 2020 Elsevier Ltd. All rights reserved.

Citation

Baichun Hu, Johnson Joseph, Xiaohui Geng, Yiheng Wu, Muhammad R Suleiman, Xinyue Liu, Jiyue Shi, Xiujun Wang, Zhicheng He, Jian Wang, Maosheng Cheng. Refined pharmacophore features for virtual screening of human thromboxane A2 receptor antagonists. Computational biology and chemistry. 2020 Jun;86:107249