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Molecular Modelling Approaches for the Analysis of Histamine Receptors and Their Interaction with Ligands

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Histamine and Histamine Receptors in Health and Disease

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 241))

Abstract

Several experimental techniques to analyse histamine receptors are available, e.g. pharmacological characterisation of known or new compounds by different types of assays or mutagenesis studies. To obtain insights into the histamine receptors on a molecular and structural level, crystal structures have to be determined and molecular modelling studies have to be performed. It is widely accepted to generate homology models of the receptor of interest based on an appropriate crystal structure as a template and to refine the resulting models by molecular dynamic simulations. A lot of modelling techniques, e.g. docking, QSAR or interaction fingerprint methods, are used to predict binding modes of ligands and pharmacological data, e.g. affinity or even efficacy. However, within the last years, molecular dynamic simulations got more and more important: First of all, molecular dynamic simulations are very helpful to refine the binding mode of a ligand to a histamine receptor, obtained by docking studies. Furthermore, with increasing computational performance it got possible to simulate complete binding pathways of ions or ligands from the aqueous extracellular phase into the allosteric or orthosteric binding pocket of histamine receptors.

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Abbreviations

E2-loop:

Extracellular loop E2

GPCR:

G protein-coupled receptor

gpH1R:

Guinea-pig histamine H1 receptor

h5-HT1BR:

Human serotonine 5-HT1B receptor

h5-HT2BR:

Human serotonine 5-HT2B receptor

hD3R:

Human dopamine D3 receptor

hH1R:

Human histamine H1 receptor

hH2R:

Human histamine H2 receptor

hH3R:

Human histamine H3 receptor

hH4R:

Human histamine H4 receptor

hM2R:

Human muscarinic M2 receptor

hβ2R:

Human adrenergic β2 receptor

MD:

Molecular dynamics

MM:

Molecular mechanics

QM:

Quantum mechanics

QSAR:

Quantitative structure activity relationship

tβ1R:

Turkey adrenergic β1 receptor

xHxR:

Different species of the four histamine receptor subtypes

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Authors and Affiliations

  1. Department of Pharmaceutical/Medicinal Chemistry II, Institute of Pharmacy, University of Regensburg, Universitäts-Str. 31, Regensburg, 93040, Germany

    Andrea Strasser & Hans-Joachim Wittmann

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  1. Andrea Strasser
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  2. Hans-Joachim Wittmann
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Correspondence to Andrea Strasser .

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  1. Department of Molecular and Medical Pharmacology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    Yuichi Hattori

  2. Institute of Pharmacology, Medical School of Hannover, Hannover, Germany

    Roland Seifert

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Strasser, A., Wittmann, HJ. (2017). Molecular Modelling Approaches for the Analysis of Histamine Receptors and Their Interaction with Ligands. In: Hattori, Y., Seifert, R. (eds) Histamine and Histamine Receptors in Health and Disease. Handbook of Experimental Pharmacology, vol 241. Springer, Cham. https://doi.org/10.1007/164_2016_113

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