Structure-and Ligand-based Study Of Histamine 2 Receptor Agonists And The EGFR Tyrosine Kinase Inhibitors

Computer-aided drug design (CADD) has been used in almost every stage of drug research and development, which changes the strategy and pipeline of drug discovery greatly. In this study, a variety of CADD methods were employed based on H2 receptor agonists and EGFR inhibitors, and useful information was obtained from both ligand and receptor sides.The first part of my job is focused on the Histamine 2 receptor (H2R), which is a member of the G-protein coupled receptors (GPCRs). In this work, a combination of structure-based and ligand-based methods, such as molecular docking, QSAR, homology modeling, and molecular dynamics were used to study the interaction between H2R and its agonists. Detailed information was obtained in this procedure, and we found some key residues, which were important for the binding of agonists. Moreover, some compounds are recommended for bioassay.The second part is about the epidermal growth factor receptor (EGFR), which is a transmembrane receptor. There are about 40 X-ray structures of the extra-membrane domain of the EGFR. Furthermore, the EGFR antagonists can be mainly divided into four clusters. Therefore, I have analyzed the recognizing abilities of EGFR structures to the antagonists in different clusters. The results demonstrated that different protein structures possessed different abilities in recognizing the antagonists in different clusters. Based on the CADD study,43 compounds were purchased from Specs database, and the 15 of them were active molecules on the cell lever. The bioassay on the enzyme lever was still in progress.