Docking and molecular dynamics study on the inhibitory activity of coumarins to aldose reductase
In order to explore the inhibitory mechanism of coumarins to aldose reductase (ARL2), AutoDock and Gromacs softwares were used for the docking and molecular dynamics studies on 14 coumarins (CM) and ARL2 protease. The docking results indicate that: residues TYR48, HIS110 and TRP111construct the active pocket of ARL2; besides Van der Waals and hydrophobic interaction, CM mainly interact with ARL2 by forming hydrogen bonds to behave their inhibitions. Except for CM1, all the other coumarins take their lactone part as acceptor to build up the hydrogen bond network with active pocket residues; unlike CM3 which has two comparable binding modes with ARL2, most coumarins only have one dominate orientation in their binding sites. The molecular dynamics calculation, based on the docking results, implies that the orientations of CM in the active pocket show different stability. Orientation of CM1 and CM3a take an unstable binding mode with ALR2, their conformations and RMSDs relative to ARL2 change a lot with dynamic process. While the rest CM are always hydrogen-bonded with residue TYR48 and HIS 110 through the carbonyl O atom of the lactone group during the whole process, they remain the original binding mode and gradually reach dynamic equilibrium.
coumarin aldose reductase AutoDock Gromacs molecular dynamics
Zhiguo Wang Baoping Ling Rui Zhang Yongjun Liu Chengbu Liu
Institute of Theoretical Chemistry, Jinan, Shandong 250100, China
国际会议
广州
英文
230-230
2008-11-01（万方平台首次上网日期，不代表论文的发表时间）