Quantum chemical calculation and binding modes of H1R; a combined study of molecular docking and DFT for suggesting therapeutically potent H1R antagonist

  • Yasir Mohamed RizaEmail author
  • Md. Rimon Parves
  • Fahmida Alam Tithi
  • Sanjida Alam
Original Research Paper


Histamine-1 receptor (H1R) belongs to the family of rhodopsin-like G-protein-coupled receptors expressed in cells that mediates allergies and other pathophysiological diseases. For alleviation of allergic symptoms, H1R antagonists are therapeutic drugs; of which the most frequently prescribed are second generation drugs, such as; Cetirizine, Loratadine, Hydroxyzine, Desloratadine, Bepotastine, Acrivastine and Rupatadine. To understand their potency, binding affinity and interaction; we have employed molecular docking and quantum chemical study such as; Induced-fit docking and calculation of quantum chemical descriptors. This study also introduces the binding site characterization of H1R, with its known antagonists and Curcumin (our proposed alternative H1R antagonist); useful for future drug target site. The interactive binding site residues of H1R are found to be; Lys-191, Tyr-108, Asp-107, Tyr-100, Lys-179, Lys-191, Thr-194, Trp-428, Phe-432, Tyr-458, Hie-450, with most of these shown to be inhibited by naturally-occurring compound curcumin. Amongst the FDA approved drugs, Hydroxyzine showed best ligand binding affinity, calculated as − 141.491 kcal/mol and naturally occurring compound, Curcumin showed binding affinity of − 87.046 kcal/mol. The known antagonists of H1R has been used for hypothesizing curcumin as naturally occurring lead compound for the target using accurate molecular docking simulation study. Though the pharmacological action of known inhibitor is already established, they could differ from their reactivity, which we have also focused in our study for predicting drug reactivity.


H1R antagonists Binding site characterization QM/MM Density functional theory Induced fit docking MM-GBSA 



We would like to express our deepest gratitude and thanks to Allah, our parents, our families, our teachers and all those who’ve helped and supported us along the way.


The authors received no funding from an external source.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval


Supplementary material

40203_2019_50_MOESM1_ESM.tif (20.6 mb)
Supplementary material 1 (TIFF 21111 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Biochemistry and Biotechnology, Faculty of Basic Medical and Pharmaceutical SciencesUniversity of Science and Technology Chittagong (USTC)ChittagongBangladesh

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