Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 17, Issue 14, Pages 4935-4942Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2009.06.003
Keywords
Bioactive conformation; DFT; QSAR; PPO; Molecular dynamic simulations
Funding
- National NSFC [20872045, 20872033]
- Research Fund for the Doctoral Program of Higher Education [20060511003]
- Hunan Provincial Natural Science Foundation of China [07JJ1003]
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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. (C) 2009 Elsevier Ltd. All rights reserved.
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