Screening of novel histone deacetylase 7 inhibitors through molecular docking followed by a combination of molecular dynamics simulations and ligand-based approach
| Autor: | Minyue Bao, Chuanfang Wu, Jinku Bao, Li Long, Zongyue Hu, Rong Sun, Yuan Yuan, Jianzong Li, Xin Long |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
030303 biophysics
Quantitative Structure-Activity Relationship Molecular Dynamics Simulation Ligands Histone Deacetylases 03 medical and health sciences Molecular dynamics Structural Biology Gene expression Transcriptional regulation Humans Molecular Biology 0303 health sciences biology Chemistry HDAC7 General Medicine Similarity computation Models Theoretical Ligand (biochemistry) Cell biology Histone Deacetylase Inhibitors Molecular Docking Simulation Histone Acetylation Drug Design biology.protein Protein Binding |
| Zdroj: | Journal of Biomolecular Structure and Dynamics. 37:4092-4103 |
| ISSN: | 1538-0254 0739-1102 |
| DOI: | 10.1080/07391102.2018.1541141 |
| Popis: | Histone acetylation/deacetylation is a key mechanism for transcription regulation which plays an important role in control of gene expression, tissue growth, and development. In particular, histone deacetylase 7 (HDAC7), a member of class IIa HDACs, is crucial to maintain cell homeostasis, and HDAC7 has emerged as a new target for cancer therapy. In this study, molecular docking was applied to screen candidate inhibitors and 21 compounds were found. Following the 50 ns molecular dynamics simulations and binding free energy calculation, ZINC00156160, ZINC01703144, ZINC04293665, and ZINC13900201 were identified as potential HDAC7 inhibitors, which would provide a sound starting point for further studies involving molecular modeling coupled with biochemical experiments. Meanwhile, similarity computation and substructure search were combined, and then we found that compounds sharing common backbone "CC(=O)N[C@@H](CSc1ccccc1)C(=O)O" could be efficient to inhibit the bioactivity of HDAC7. Then comparative molecular similarity indices analysis (CoMSIA) techniques were implemented to investigate the relationship between properties of the substituent group and bioactivities of small molecules. The CoMSIA model exhibited powerful predictivity, with satisfactory statistical parameters such as |
| Databáze: | OpenAIRE |
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