Computerized modeling techniques predict the 3D structure of H₄R: facts and fiction.
The functional characterization of proteins presents a daily challenge r biochemical, medical and computational sciences, especially when the structures are undetermined empirically, as in the case of the Histamine H4 Receptor (H₄R). H₄R is a member of the GPCR superfamily that plays a vital role in immune and inflammatory responses. To date, the concept of GPCRs modeling is highlighted in textbooks and pharmaceutical pamphlets, and this group of proteins has been the subject of almost 3500 publications in the scientific literature. The dynamic nature of determining the GPCRs structure was elucidated through elegant and creative modeling methodologies, implemented by many groups around the world. H₄R which belongs to the GPCR family was cloned in 2000; understandably, its biological activity was reported only 65 times in pubmed. Here we attempt to cover the fundamental concepts of H₄R structure modeling and its implementation in drug discovery, especially those that have been experimentally tested and to highlight some ideas that are currently being discussed on the dynamic nature of H₄R and GPCRs computerized techniques for 3D structure modeling.
Drug Discovery Informatics Lab, QRC-Qasemi Research Center,Al-Qasemi Academic College, POB 124, Baka El-Garbiah 30100, Israel.
Hilal
H
Zaid
Siba
S
Ismael-Shanak
Amit
A
Michaeli
Anwar
A
Rayan
D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D055808:Drug Discovery; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D011968:Receptors, Histamine / Q000737:chemistry* / Q000235:genetics; D000074040:Receptors, Histamine H4; D017386:Sequence Homology, Amino Acid
C418607:HRH4 protein, human; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4