PMC:3480680 / 613-2627 JSONTXT

{"project":"2_test","denotations":[{"id":"23105941-12750740-44845710","span":{"begin":123,"end":124},"obj":"12750740"},{"id":"23105941-16714488-44845711","span":{"begin":126,"end":127},"obj":"16714488"},{"id":"23105941-10720314-44845712","span":{"begin":273,"end":274},"obj":"10720314"},{"id":"23105941-17962520-44845713","span":{"begin":906,"end":907},"obj":"17962520"},{"id":"23105941-21097933-44845713","span":{"begin":906,"end":907},"obj":"21097933"},{"id":"23105941-21697825-44845713","span":{"begin":906,"end":907},"obj":"21697825"},{"id":"23105941-20636392-44845714","span":{"begin":1344,"end":1345},"obj":"20636392"},{"id":"23105941-1846044-44845714","span":{"begin":1344,"end":1345},"obj":"1846044"},{"id":"23105941-2164693-44845714","span":{"begin":1344,"end":1345},"obj":"2164693"},{"id":"23105941-9311023-44845714","span":{"begin":1344,"end":1345},"obj":"9311023"},{"id":"23105941-15034588-44845715","span":{"begin":1620,"end":1622},"obj":"15034588"},{"id":"23105941-15534702-44845716","span":{"begin":1624,"end":1626},"obj":"15534702"}],"text":"Introduction\nG protein-coupled receptors (GPCRs) are regarded to take up more than one-fourth of marketed human medicines [1, 2]. Drugs targeting GPCRs account for the majority of the best-selling drugs and about 40% of all prescription pharmaceuticals in the marketplace [3].\nHistamine receptors belong to one family of rhodopsin-like class A GPCRs, and four subtypes are named in chronological order as H1, H2, H3, and H4. Histamine exerts its effects through the activation of these four histamine receptors. Each type of histamine receptor reacts to subtype-specific ligands into an active or inactive form.\nGPCRs are integral membrane proteins that consist of 7 transmembrane segments connected by 3 intracellular and 3 extracellular loops of variable length. The crystal structures of GPCRs with their binding ligands have revealed the features of the ligand binding pockets and extracellular loops [4-6]. A ligand of GPCR activates the receptor by changing the receptor structure to the active form.\nThe biogenic amine histamine [2-(1H-imidazol-5-yl) ethanamine] (Fig. 1) is produced by decarboxylation of L-histidine and acts as a chemical mediator and neurotransmitter in central and peripheral tissues. It acts as an important pharmacological modulator involved in the processes of allergy, inflammation, neurophysiology, and cancer [7-10].\nThe molecular understanding of ligand-receptor interactions of GPCR remains unclear and is still the subject of investigations. There are several theories explaining the ligand-receptor interaction mechanism, such as shape theory, binding theory, and vibration theory [11, 12]. The structures of histamine receptor ligands are so variable that we can not easily classify the pharmacological function of the ligand. To find any other characteristic in the molecular patterns between agonists and antagonists of histamine receptors, a computational approach to molecular vibration was carried out in an attempt to find a bit of the molecular interaction mechanisms."}