| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
The endonuclease activity which lies in influenza polymerase acidic protein N-terminal domain (PAN) is a potent target for novel antiviral agents. We identified some novel inhibitors for PAN endonuclease activity. The binding mode of the inhibitory compounds to PAN was closely investigated by means of X-ray crystal structure analysis and molecular dynamics (MD) simulation. It was observed in the crystal structure that three molecules of the same kind of the inhibitor were bound to one PAN. Hence, the stability of inhibitor binding was examined by performing 100 ns MD simulation. During the MD simulation, three inhibitor molecules fluctuated at the respective binding site while all the molecules maintained interactions with the protein. MM/GBSA analysis suggested that the molecule located apart from the metal chelated site has a higher affinity than the others. Structural information of this study will provide a hint for designing and developing potent agents against influenza viruses.
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