Identification of nonplanar small molecule for G-quadruplex grooves: molecular docking and molecular dynamic study.
DNA G-quadruplex is an attractive drug target for anticancer therapy. Most G-quadruplex ligands have little selectivity, due to π-stacking interaction with common G-tetrads surface. Thanks to the varieties of G-quadruplex grooves, the groove-binding ligand is expected to create high selectivity. Therefore, developing novel molecular geometries that target G-quadruplex groove has been paid growing attention. In this work, steroid FG, a special nonplanar and nonaromatic small molecule, interacting with different conformations of G-quadruplexes has been studied by molecular docking and molecular dynamics simulations. The results showed the selectivity of the hydrophobic group of steroid FG for the wide groove of antiparallel G-quadruplex. The methyl groups on the tetracyclic ring of steroid represent the specific binding ability for the small hydrophobic cavity formed by reversed stacking of G-tetrads in antiparallel G-quadruplex groove. This work provides new insight for developing new classes of G-quadruplex groove-binding ligands.
Department of Chemistry, College of Science, Yanbian University, Yanji, PR China.
Jinlian
J
Li
Xiaoqiang
X
Jin
LiHong
L
Hu
Jianping
J
Wang
Zhongmin
Z
Su
D054856:G-Quadruplexes; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D013256:Steroids / Q000737:chemistry*
D013256:Steroids