AI Article Synopsis
- This study investigates how the structure of epigenetic inhibitors affects their ability to target the lysine methyltransferase G9a, using advanced techniques like activity landscape analysis, molecular docking, and dynamics simulations.
- Researchers analyzed data from 251 G9a inhibitors to identify patterns in how molecular structure correlates with activity, highlighting the discovery of important interactions with specific amino acids.
- The findings aim to improve the understanding and development of targeted G9a inhibitors, which could have implications in epigenetic research and therapeutic strategies.
Article Abstract
In this work, we analyze the structure-activity relationships (SAR) of epigenetic inhibitors (lysine mimetics) against lysine methyltransferase (G9a or EHMT2) using a combined activity landscape, molecular docking and molecular dynamics approach. The study was based on a set of 251 G9a inhibitors with reported experimental activity. The activity landscape analysis rapidly led to the identification of activity cliffs, scaffolds hops and other active an inactive molecules with distinct SAR. Structure-based analysis of activity cliffs, scaffold hops and other selected active and inactive G9a inhibitors by means of docking followed by molecular dynamics simulations led to the identification of interactions with key residues involved in activity against G9a, for instance with ASP 1083, LEU 1086, ASP 1088, TYR 1154 and PHE 1158. The outcome of this work is expected to further advance the development of G9a inhibitors.
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