Abstract
A group of class I selective HDAC inhibitors were derived previously, with inhibitory preference of HDAC1 and HDAC3 over HDAC2. Molecular docking and molecular dynamic simulation approaches were performed to elucidate the structural basis of inhibitor’s selectivity between HDAC2 and HDAC3. Superimposition of the rigid docked structures showed that residues in the active sites of both receptors are identical, and the inhibitor (D18) has similar binding patterns in both sites. Results of the flexible docking suggested that strong hydrophobic interactions between molecule D18 and Phe199 play significant role in the selectivity. The interactions were verified to be stable by further molecular dynamic simulation processes.
Keywords: HDAC, inhibitor, selectivity, flexible docking, molecular dynamic simulation.
Letters in Drug Design & Discovery
Title:Molecular Simulation of HDAC1/3 Inhibitor: Insights into the Structural Basis of Selectivity
Volume: 13 Issue: 1
Author(s): Lei Zhang and Lihui Zhang
Affiliation:
Keywords: HDAC, inhibitor, selectivity, flexible docking, molecular dynamic simulation.
Abstract: A group of class I selective HDAC inhibitors were derived previously, with inhibitory preference of HDAC1 and HDAC3 over HDAC2. Molecular docking and molecular dynamic simulation approaches were performed to elucidate the structural basis of inhibitor’s selectivity between HDAC2 and HDAC3. Superimposition of the rigid docked structures showed that residues in the active sites of both receptors are identical, and the inhibitor (D18) has similar binding patterns in both sites. Results of the flexible docking suggested that strong hydrophobic interactions between molecule D18 and Phe199 play significant role in the selectivity. The interactions were verified to be stable by further molecular dynamic simulation processes.
Export Options
About this article
Cite this article as:
Zhang Lei and Zhang Lihui, Molecular Simulation of HDAC1/3 Inhibitor: Insights into the Structural Basis of Selectivity, Letters in Drug Design & Discovery 2016; 13 (1) . https://dx.doi.org/10.2174/1570180812666150630183816
DOI https://dx.doi.org/10.2174/1570180812666150630183816 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The Applications of Biomarkers in Early Clinical Drug Development to Improve Decision-Making Processes
Current Clinical Pharmacology Lewy Bodies: A Spectator or Salient Killer?
CNS & Neurological Disorders - Drug Targets Metalloprotein Inhibitors for the Treatment of Human Diseases
Current Topics in Medicinal Chemistry Targeted Lipid Nanoparticles for Antisense Oligonucleotide Delivery
Current Pharmaceutical Biotechnology Current Prodrug Strategies for the Delivery of Nucleotides into Cells
Drug Design Reviews - Online (Discontinued) Antibody Therapy of Acute and Chronic Leukemias
Current Pharmaceutical Biotechnology Fingerprint-based 2D-QSAR Models for Predicting Bcl-2 Inhibitors Affinity
Letters in Drug Design & Discovery Rational Design of CPP-based Drug Delivery Systems: Considerations from Pharmacokinetics
Current Pharmaceutical Biotechnology Plant-Made Antibodies: Properties and Therapeutic Applications
Current Medicinal Chemistry Nitrogen Mustards as Anticancer Chemotherapies: Historic Perspective, Current Developments and Future Trends
Current Topics in Medicinal Chemistry Histone Modifier Differentially Regulates Gene Expression and Unravels Survival Role of MicroRNA-494 in Jurkat Leukemia
MicroRNA CX-4945, a Selective Inhibitor of Casein Kinase 2, Synergizes with B Cell Receptor Signaling Inhibitors in Inducing Diffuse Large B Cell Lymphoma Cell Death
Current Cancer Drug Targets Rhinocerebral Mucormycosis with Orosinusal Involvement: Diagnostic and Surgical Treatment Guidelines
Endocrine, Metabolic & Immune Disorders - Drug Targets Monoclonal Antibody “Gold Rush”
Current Medicinal Chemistry Altered Expression of MicroRNAs in the Bone Marrow of Multiple Myeloma Patients and their Relationship to Cytogenetic Aberrations
Current Pharmaceutical Biotechnology Gene Therapy: The First Approved Gene-Based Medicines, Molecular Mechanisms and Clinical Indications
Current Molecular Pharmacology Manipulation of Glycolysis in Malignant Tumors: Fantasy or Therapy?
Current Medicinal Chemistry Lessons we Learned from High-Throughput and Top-Down Systems Biology Analyses about Glioma Stem Cells
Current Pharmaceutical Design Adhesion Molecules in Lung Cancer: Implications in the Pathogenesis and Management
Current Pharmaceutical Design Targeted Therapies in Combination with Radiotherapy in Oesophageal and Gastroesophageal Carcinoma
Current Medicinal Chemistry