Toward in silico structure-based ADMET prediction in drug discovery

Gautier Moroy, Virginie Y. Martiny, Philippe Vayer, Bruno O. Villoutreix, Maria A. Miteva
2012 Drug Discovery Today  
Quantitative structure-activity relationship (QSAR) methods and related approaches have been used to investigate the molecular features that influence the absorption, distribution, metabolism, excretion and toxicity (ADMET) of drugs. As the three-dimensional structures of several major ADMET proteins become available, structure-based (docking-scoring) computations can be carried out to complement or to go beyond QSAR studies. Applying docking-scoring methods to ADMET proteins is a challenging
more » ... ocess because they usually have a large and flexible binding cavity; however, promising results relating to metabolizing enzymes have been reported. After reviewing current trends in the field we applied structure-based methods in the context of receptor flexibility in a case study involving the phase II metabolizing sulfotransferases. Overall, the explored concepts and results suggested that structure-based ADMET profiling will probably join the mainstream during the coming years. Reviews INFORMATICS Corresponding author:. Miteva, M.A. ( 44
doi:10.1016/j.drudis.2011.10.023 pmid:22056716 fatcat:jiela55gcra6zpwhsbttc7d64i