バーチャルスクリーニングによる細菌RNAポリメラーゼを標的とした新規抗菌剤の探索

Chem-Bio Informatics Journal

上條 俊介¹  小野�? 賢司¹  川崎 平康¹ 

[1] 東京大学生産�?術研究所

关键词: Docking;    ドッキング;    virtual screening;    バーチャルスクリーニング;    scoring function;    スコア関数;    score optimization;    �?適化;    antibiotics;    抗菌剤;   

DOI  :  10.1273/cbij.11.52

学科分类：生物化学/生物物理

来源: Chem-Bio Informatics Society

【 摘 要 】

References(20)Cited-By(1)Bacterial RNA polymerase (RNAP) is the least popular target for antibiotics, and currently Rifampicin is only an approved drug for clinical use. However, RNAP is essential for bacterial growth and survival, and it can be a promising target for antimicrobial agents. Thus, we decided to search new antimicrobial agents for RNAP by virtual screening. When virtual screenings are performed, certain compounds repeatedly appears on hits covering a wide range of targets (frequently hitters). Also, the performance of hit generation is important factor in success of the virtual screening. Since we previously developed the optimized docking scores, we examined our scoring methods with rigorous removals of frequent hitters. We used two complex structures for RNAP, and also used two unrelated structures as negative controls to remove frequent hitters. Finally, we selected seven high-scored candidates from hits, and two of them showed the inhibition of Gram-positive bacteria by paper disk agar diffusion assay in vivo.

【 授权许可】

Unknown