Molecular Docking Study Of Six Pyrimidine Derivatives As Egfr (EPIDERMAL Growth Factor Receptor) And Ca Ix (CARBONIC Anhydrase Ix) Inhibitor

Objective: The present study was carried out to discover whether these pyrimidine derivatives have the potential to be used as epidermal growth factor receptor (EGFR) and carbonic anhydrase (CA) IX inhibitors through structure-based in silico study. Methods: Docking was performed on 6 pyrimidine analogs; cetuximab and curcumin were taken as reference drug. The structure of the target protein retrieved from the RCSB Protein databank and the protein-ligand docking was performed using Pyrx AutoDock wizard with MGL tools 1.5.6 by using Lamarckian algorithm. Results: All the compounds have shown lower binding energy and inhibition constant (Ki) value than reference drug cetuximab and curcumin. Out of the 6 inhibitors analyzed vkh has shown minimum binding energy against the target protein EGFR and CA IX respectively. Smaller Ki value shows stronger interaction. The scoring value of the interaction of vkh i. e-10.74 and-9.93 Kcal/mol and Ki 13.17ɳM and 53.04ɳM against the target protein EGFR and CA IX respectively while the reference drug cetuximab has shown binding energy-6.09 Kcal/mol with Ki value 34.44 µM and curcumin has shown binding energy-6.02 kcal/mol with Ki value 38.60 µM. Conclusion: It can be concluded that the molecule vkh could have potential to be used as an EGFR inhibitor and CA IX inhibitor.

Discovery of Protease Inhibitors of HIV-1 through Structure Based Virtual Screening / 昆明医科大学学报

Objective Through new virtual screening tools of PyRx to run AutoDock Vina to virtually screen the 20000 compounds in ZINC database,so as to discover new HIV protease inhibitors, and make a tentative study of the combination model of them with HIV protease. Methods The study focused on the targets of HIV protease, the virtual screening program of AutoDock Vina was used to virtually screen the compounds in ZINC database. It was differing from previous studies by using new virtual screening tools of PyRx to run AutoDock Vina. The HIV protease crystal structure (PDB ID:4phv) was downloaded from PDB and dealed with AutoDock Tools. Compound structure was downloaded from ZINC database and imported with PyRx, processed into format of pdbqt. The post-screen compounds were imported into AutoDockTools, and the data were outputted with PyMOL.Results There were 1000 drugs of small molecular compound for high-throughput screening from about 20000 compounds in the library. After screening for 3 times we found five highly active HIV protease inhibitors from the 1000 small molecular compounds.Conclusion The further development of the five new HIV protease inhibitors will contribute to the treatment and basic research of HIV,and provide new reference for structure-based virtual screening and discovery of HIV drugs.