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Updated: May 23, 2026
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Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
Published on: August 10, 2017
Insights from comprehensive multiple receptor docking to HDAC8
Michael Brunsteiner1, Pavel A Petukhov
1Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
Journal of Molecular Modeling
|March 21, 2012
Summary
This study investigated HDAC8 crystal structures and docking methods. Ligands with flexible groups bind better to open HDAC8 conformations, explaining why pyrazole inhibitors outperform isoxazole ones.
Area of Science:
- Biochemistry
- Structural Biology
- Medicinal Chemistry
Background:
- Histone deacetylase 8 (HDAC8) is a validated target for therapeutic intervention.
- Understanding the structural basis of HDAC8 inhibition is crucial for drug design.
Purpose of the Study:
- To systematically investigate HDAC8 crystal structures and the impact of various docking protocols.
- To rationalize the observed differences in potency between pyrazole-based and isoxazole-based HDAC8 inhibitors.
Main Methods:
- Computational analysis of available HDAC8 crystal structures.
- Molecular docking simulations using different receptor structures and protocols.
Main Results:
- The open conformation of HDAC8 is favored by ligands possessing flexible surface binding groups.
- This open conformation facilitates ligand binding by minimizing solvent exposure.
- The findings rationalize the superior potency of pyrazole-based inhibitors over isoxazole-based ones.
Conclusions:
- Ligand flexibility and HDAC8 conformation are key determinants of binding affinity.
- The study provides structural insights for the design of more potent HDAC8 inhibitors.
