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In silico binding characteristics between human histamine H1 receptor and antagonists

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Abstract

It is widely acknowledged that the H1 receptor antagonists have important therapeutic significance in the treatment of various allergic disorders, but little was known about the binding mode between the receptor and antagonists since the crystal structure of G-protein coupling receptors (GPCRs) were hard to obtain. In this paper, a theoretical three-dimensional model of human histamine H1 receptor (HHR1) was developed on the basis of recently reported high resolution structures of human A2A adenosine receptor, human β2-adrenoceptor and turkey β1-adrenoceptor. Furthermore, three representative H1 receptor antagonists were chosen for docking studies. Subsequently, a qualitative pharmacophore model was developed by Hiphop algorithm based on the docking conformations of these three antagonists. In this paper, active environment, certain key residues, and the corresponding pharmacophore features of H1 receptor were identified by such combinations of receptor-based and ligand-based approaches, which would give sufficient guidance for the rational design of novel antihistamine agents.

Active environment, certain key residues and the corresponding pharmacophore features of H1 receptor were identified by such a combination of receptor-based and ligand-based approaches, which would give sufficient guidance for the rational design of novel antihistamine agents.

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Authors and Affiliations

  1. School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China

    Xiaojian Wang, Qian Yang & Qidong You

  2. Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Jinan, Shandong, 250012, China

    Minyong Li

  3. Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China

    Xiaojian Wang & Dali Yin

Authors
  1. Xiaojian Wang
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  2. Qian Yang
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  3. Minyong Li
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  4. Dali Yin
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  5. Qidong You
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Corresponding authors

Correspondence to Minyong Li or Qidong You.

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Tables S1-2

For pharmacophore external validation (DOC 463 kb)

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Wang, X., Yang, Q., Li, M. et al. In silico binding characteristics between human histamine H1 receptor and antagonists. J Mol Model 16, 1529–1537 (2010). https://doi.org/10.1007/s00894-010-0666-z

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  • DOI: https://doi.org/10.1007/s00894-010-0666-z

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