title: Bioactive conformation analysis of cyclic imides as protoporphyrinogen oxidase inhibitor by combining DFT calculations, QSAR and molecular dynamic simulations.
abstract: 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.
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, Central China Normal University, Wuhan 430079, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Ge-Fei
authors.initials: GF
authors.lastname: Hao
authors.forename: Yin
authors.initials: Y
authors.lastname: Tan
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xi
authors.forename: Ming-Zhi
authors.initials: MZ
authors.lastname: Huang
authors.forename: Guang-Fu
authors.initials: GF
authors.lastname: Yang
mesh_terms: 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
chemical_list: D007094:Imides; D050768:Protoporphyrinogen Oxidase