Bioactive conformation analysis of cyclic imides as protoporphyrinogen oxidase inhibitor by combining DFT calculations, QSAR and molecular dynamic simulations.
Bioorg Med Chem
; 17(14): 4935-42, 2009 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-19540767
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Relação Quantitativa Estrutura-Atividade
/
Protoporfirinogênio Oxidase
/
Imidas
Limite:
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article