Molecular docking and 3D-QSAR studies on inhibitors of DNA damage signaling enzyme human PARP-1.
Poly (ADP-ribose) polymerase-1 (PARP-1) operates in a DNA damage signaling network. Molecular docking and three dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed on human PARP-1 inhibitors. Docked conformation obtained for each molecule was used as such for 3D-QSAR analysis. Molecules were divided into a training set and a test set randomly in four different ways, partial least square analysis was performed to obtain QSAR models using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Derived models showed good statistical reliability that is evident from their r², q²(loo) and r²(pred) values. To obtain a consensus for predictive ability from all the models, average regression coefficient r²(avg) was calculated. CoMFA and CoMSIA models showed a value of 0.930 and 0.936, respectively. Information obtained from the best 3D-QSAR model was applied for optimization of lead molecule and design of novel potential inhibitors.
Molecular Modeling and Medicinal Chemistry Group, Department of Chemistry, Nizam College, Osmania University, Basheerbagh, Hyderabad, India.
Sabiha
S
Fatima
Raju
R
Bathini
Sree Kanth
SK
Sivan
Vijjulatha
V
Manga
D004249:DNA Damage; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D016018:Least-Squares Analysis; D008958:Models, Molecular; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D015398:Signal Transduction / Q000187:drug effects; D055672:Static Electricity
D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases