Drug metabolism studies play a critical role in the optimization of the therapeutic efficacy of newer drug
candidates. Many drug candidates and drugs were withdrawn from the pre-clinical/clinical stage or market due to the
poor metabolic profiles. The poor metabolic profiles may make the clinical candidates/drugs inactive or toxic. Therefore,
it is necessary to optimize the metabolic profiles at the initial phase of drug discovery and development processes.
Recently, molecular modeling approaches were found to be useful in the optimization of metabolic profiles of
clinical candidates. The molecular modeling approaches were employed in the identification of various metabolic
profiles. In the present study, the current status of the research work on drug metabolism based on molecular modeling
methodologies has been reviewed. The basics of drug metabolism and its importance in the physiological process
of the human body have been described. Moreover, the involvement of molecular modeling approaches like pharmacophore-
based modeling, QSAR, molecular docking, virtual screening, quantum chemical analysis, molecular dynamics,
etc., in predicting metabolic profiles of therapeutic agents is analyzed. The present review provides computational
insights in the prediction of substrate specificity, metabolic activity, SOM, metabolites, toxicity, etc., on cytochrome
P450-mediated drug metabolism. The study may help the researchers to design novel drug candidates for the
various classes of therapeutic targets with efficient metabolic profiles.