ABSTRACT
Cytochromes P450 (CYPs) constitute the most important family of biotransformation enzymes and play an important role in the disposition of drugs and their pharmacological and toxicological effects. Early consideration of absorption disposition, metabolism, and excretion (ADME) properties is increasingly seen as essential for efficient discovery and development of new drugs and drug candidates. The state-of-the-art computational methods used in CYP modeling vary considerably, as does the reliability of the results obtained. Protein homology modeling in combination with automated docking and molecular dynamics simulations have been used successfully for the rationalization and prediction of metabolite formation by several CYP isoenzymes. Evaluation of different scoring functions, docking algorithms and pooling of docking results from different docking algorithms, has recently been shown to be critical in obtaining good results for ligand docking in CYP crystal structures and also to make docking into homology model structures feasible.
