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

• Published in: Handbook of experimental pharmacology Vol. 241; pp. 31 - 61
• Main Authors: Strasser, Andrea, Wittmann, Hans-Joachim
• Format: Book Chapter Journal Article
• Language: English
• Published: Switzerland Springer International Publishing AG 01.01.2017; Springer International Publishing
• Series: Handbook of Experimental Pharmacology
• Subjects: Amino Acid Sequence; Binding Sites - physiology; Biochemistry; Histamine receptors; Homology modelling; Humans; Ligands; Models, Molecular; Molecular dynamics; Molecular Dynamics Simulation; Molecular modelling; Neurosciences; Pharmacology; Protein Conformation; Receptors, Histamine - chemistry; Receptors, Histamine - metabolism; Structure-Activity Relationship; Histamine receptors; Molecular dynamics; Molecular modelling; Homology modelling
• ISBN: 9783319581927; 3319581929
• ISSN: 0171-2004; 1865-0325
• DOI: 10.1007/164_2016_113

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.