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Adaptable Small Ligand of CYP1 Enzymes for Use in Understanding the Structural Features Determining Isoform Selectivity.

ABSTRACT: 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.

SUBMITTER: Lee JY

PROVIDER: S-EPMC6295865 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Adaptable Small Ligand of CYP1 Enzymes for Use in Understanding the Structural Features Determining Isoform Selectivity.

Lee Joo-Youn JY Cho Hyunkyung H Thangapandian Sundarapandian S Lim Chaemin C Chun Young-Jin YJ Lee Yoonji Y Choi Sun S Kim Sanghee S

ACS medicinal chemistry letters 20181029 12

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 C ...[more]

PMID: 30613334

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