Bioactive conformation analysis of cyclic imides as protoporphyrinogen oxidase inhibitor by combining DFT calculations, QSAR and molecular dynamic simulations.
Bioactive conformation of drugs is one of the key points for understanding the ligand-receptor interactions. In the present study, by combining density functional theory-based (DFT-based) conformation analysis with quantitative structure-activity relationship analysis (QSAR), we developed successfully a new approach (DFT/QSAR) to carry out bioactive conformation analyses for a series of 25 cyclic imide derivatives as protoporphyrinogen oxidase (PPO) inhibitors. Further potential energy surface scan, molecular docking and molecular dynamic simulation calculations validated that the DFT/QSAR-derived conformation is indeed very similar to the 'real' bioactive conformation. We believe the DFT/QSAR approach provides a simple alternative for the bioactive conformation of small molecules, especially in the case that the three-dimensional structure of protein is unknown.
Zhang
Li
L
Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, Central China Normal University, Wuhan 430079, PR China.
Hao
Ge-Fei
GF
Tan
Yin
Y
Xi
Zhen
Z
Huang
Ming-Zhi
MZ
Yang
Guang-Fu
GF
D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D007094:Imides / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011485:Protein Binding; D050768:Protoporphyrinogen Oxidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D011789:Quantum Theory
D007094:Imides; D050768:Protoporphyrinogen Oxidase