Insights into the stereoselectivity of human SETD7 methyltransferase

Chirality has an important role in the drug design because enantiomers may exhibit different bioactivity when interacting with macromolecules of a living organism. In our previous work, based on the analysis of a set of 100 chiral drugs, a relationship was established between the sign of chirality of enantiomers and their bioactivity. To understand the reasons for the observed patterns of chiral specificity of drug enantiomers, the interaction of 10 enantiomeric pairs of chiral drugs with the corresponding target proteins has been considered using molecular docking and further postprocessing by quantum chemistry methods. The data obtained confirm that the energetic aspect of the interaction between opposite enantiomers and target protein affects the enantiomer biological activity. In addition, the results show that molecular docking is able to distinguish between bioactive and inactive/less active enantiomers, although many docking programs are not accurate enough to distinguish a weak inhibitor from a strong one.

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Identification of potential ATP-competitive cyclin-dependent kinase 1 inhibitors: De novo drug generation, molecular docking, and molecular dynamics simulation

Wang

et al. 2023

Computers in Biology and Medicine

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Insights into the stereoselectivity of human SETD7 methyltransferase

Abstract: This work clearly reveals the interaction of SAM/hSET7/(R/S)-PFI-2 systems, and confirms that the different bioactive energy barriers of (R)-PFI-2 and (S)-PFI-2 lead to the tremendously different inhibitory activities between these two antipodes.

Cited by 4 publications

References 31 publications

Lysine methyltransferase inhibitors: where we are now

Lysine methyltransferase inhibitors: where we are now

Molecular Docking of Chiral Drug Enantiomers With Different Bioactivities

Identification of potential ATP-competitive cyclin-dependent kinase 1 inhibitors: De novo drug generation, molecular docking, and molecular dynamics simulation

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