Summary: | 碩士 === 國立臺灣師範大學 === 化學系 === 98 === Protein kinase A (PKA) is a kinase protein that has several functions in cell, including regulation of glycogen, sugar, and lipid metabolism. It also plays significant role in a number of biochemical reaction networks associated with diseases, including lung cancer and colorectal cancers. In the present study, we used docking computation to aid in design and discovery of PKA inhibitors. First, we carried out docking computations for 20 PKA-inhibitor complexes from protein data bank to examine their reproducibility. The results showed that the computed fitnesses values of ligands are in good accord with the experimental IC50 values. Second, crossing docking of selected 5 complexes was carried out to investigate if and how ligand conformations can be regained when a protein structure from different complexes were used. In addition, thirdly, the protein structures from these 5 complexes were used to undergo a virtual screening to see if 10 active compounds can be screened out of 1000 compounds selected from a database. In these computations, the several side chains at active site were allowed to move to examine how this effect affects the docking results. The results showed that better results were obtained in the case of allowing 4 residues to move. Finally, a virtual screening for 24535 compounds was carried out. The interactions between top-ranked compounds and PKA were analyzed and discussed. These computed results and analysis should be of aid in design and discovery of PKA inhibitors.
|