Although several families of compounds have been identified as scaffolds for inhibitors of the CYP1 family, the isoform selectivity determining structural features has not been fully clarified at the molecular interaction level. We studied the CYP1 isoform selectivity for stilbenoid inhibitors using integrated induced fit docking and molecular dynamics simulations. The hydrophobic interactions with the specific phenylalanine residues in the F helix are correlated with inhibitory potency in the CYP1 family. Through this study, we found that the adaptable, small, and semirigid ligand is a promising starting point for the development of isoform-selective inhibitors and investigation of selectivity-determining features.
Bibliographical noteFunding Information:
This work was supported by the Mid-Career Researcher Program (NRF-2016R1A2A1A05005375) of the National Research Foundation (NRF) grant funded by the Korea government (MSIP).
© 2018 American Chemical Society.
- Cytochrome P450
- Isoform selectivity
- Molecular dynamics