The Prediction Of Amine Receptors Ligand-binding Region And Sites

The amine receptor is a subfamily of rhodopsin like receptors, which belongs to G protein coupled receptors. Based on sequence-derived and binding data, amine receptor can be classified seven subfamilies, which are as follows: acetylcholine receptor, adreno receptor, dopamine receptor, histamine receptor, octopamine receptor, serotonin receptor and trace amine receptor. These subfamilies of amine receptors show some common features in their structure, including a N and C terminus, a bundle of seven transmembrane alpha helices connected by three alternating extracellular(ECL1→ECL3) and intracellular(ICL1→ICL4) peptide loops. Amine plays a very important role in drug design and mainly to stimulate nerve with the help of relevant receptors. The principal question in drug design is how to study the ligand-binding sites and others because of the poor structure information. In the past, the Affinity Labeling and Site-Directed Mutagenesis are the primary methods to study amine receptor. However, Affinity Labeling and Site-Directed Mutagenesis have certain disadvantages due to the limited number of affinity reagents and indirect effects of mutations on function. In order to circumvent the limitations, bioinformatics are used to study the amine receptor. Furthermore, it also direct the follow up study..In order to get better understanding about the combining mechanism of biological amine receptor, the variability, hydrophobicity and conservation are analyzed in the present study. The results show that E- Ⅱ may participate in the ligand-binding through entering into the crack formed by TM, which is different from that of only TM participate in. This mechanism is similar to that of the ligand of rhodopsin like receptor. TM3, TM5 and TM7 are highly water-soluble and considered as the ligand-binding sites as showed by the analysis of its hydrophobicity. The 2D helix cross section model was constructed by integrating the variability, hydrophobicity and conservation with whole structure, and the potential ligand-binding region Ⅰ ,Ⅱ were also figured out. Sites of TM3 and TM7 located in the center area of ligand-binding, which toward crack are conservational and water-soluble, may play a key role of maintaining the structure during the process of ligand-binding for the more interface with Ⅰ , Ⅱ. On the contrary, TM4 is assumed to playa key role in the ligand-binding for the high variability. The motifs of amine receptor and sub-receptors were mined respectively. In addition, the concept of family variable but sub-family conserved(FVSC) motifs were introduced. FVSC motifs are conserved in the sub-receptors but variable in the father receptor, they also considered to play a key role in the binding function of sub-receptor. Finally, the individual motifs and corresponding sites carrying the function of ligand-binding were analyzed to combine the analysis from global level and local level, the results have the highly accuracy and coherence compared to the mutation experiment.