นโยบายงานวิจัย /จรรยาบรรณนักวิจัย /ระดับคุณภาพบทความวิจัยตีพิมพ์ /ระดับคุณภาพผลงานวิชาการ /แหล่งทุน /ดาวน์โหลด /ฐานข้อมูลวิจัย /วิเคราะห์-สังเคราะห์งานวิจัย /ลิขสิทธิ์ /ข่าว


Insight into the crucial binding mode and binding interaction of 4-aminoquinoline derivatives with  M. tuberculosis GyrB using MD simulation and binding free energy calculation  (Proceeding and Poster)


Author

-

Naruedon Phusi1, Bunrat Tharat1, Chayanin Hanwarinroj1, Kampanart Chayajaras1, Nitima Suttipanta2, Pharit Kamsri3, Auradee Punkvang3, Patchareenart Saparpakorn4, Supa Hannongbua4, Khomson Suttisintong5 and Pornpan Pungpo


Journal

- The 8th Thailand-Japan International Academic Conference 2016

Volume

- 8

Year

- 2016

Publication type

-

Page list

- 101-105

Abstract

   

 Mycobacterial DNA gyrase B subunit has been identified to be one of the potentially underexploited drug targets in the field of antitubercular drug discovery. A series of novel 4-aminoquinoline derivatives were developed as potential GyrB inhibitors.  In the present study, we applied MD simulations to elucidate the binding site of 4-aminoquinoline derivatives in the GyrB pocket. Based on the obtained MD simulations, the results indicate that compound 1, the highest active compound, could form hydrogen bond interactions with residues Asn52 in the GyrB pocket as compared to other compounds. Moreover, electrostatic and hydrophobic interactions are also important for binding affinities. Based on rational design novel 4-aminoquinoline derivatives, design compounds showed strong hydrogen bond interactions with amino acids in GyrB binding pocket. Consequently, the obtained results from this study provide informative structural concept for designing of novel 4-aminoquinoline derivatives with better potency against Gyr


Keywords

   

4-Aminoquinoline derivatives, GyrB, anti-TB agents, MD simulations