Background: Molecular docking has often been used before to calculate in silico
affinity of drugs towards their molecular target, but not to estimate leading CYP isoform
responsible for metabolism of studied compounds.
Objective: The aim of this study is to present molecular docking as a valid alternative for costly in
vitro studies resulting in estimation of leading CYP isoform.
Methods: In vitro part was based on incubations of studied compounds with isolated CYP3A4
isoform followed by LC-MS analysis. The in silico stage consisted of docking three-dimensional
models of the studied compounds with a three-dimensional model of the leading metabolizing
isoform (CYP3A4), which was designated during the in vitro part of the study. XenoSite P450
metabolism prediction was also used to predict sites of metabolism and calculate probability
Results: The calculated affinities showed a clear similarity when the in vitro results were compared
with the calculated in silico affinity values. XenoSite CYP3A4 metabolism probability values also
confirm significant participation of CYP3A4 in metabolism of studied compounds.
Conclusion: Both molecular docking and XenoSite P450 metabolism prediction provide data that
stands in agreement with in vitro studies, granting a more detailed spectrum on predicting CYP3A4
metabolism, and presenting molecular docking as a promising tool to cut costs and increase
effectiveness in early drug development stages.