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Identification of Inhibitor Binding Site in Human Sirtuin 2 Using Molecular Docking and Dynamics Simulations
- Source :
- PLoS ONE, PLOS ONE(8): 1, PLoS ONE, Vol 8, Iss 1, p e51429 (2013)
- Publication Year :
- 2013
- Publisher :
- Public Library of Science, 2013.
-
Abstract
- The ability to identify the site of a protein that can bind with high affinity to small, drug-like compounds has been an important goal in drug design. Sirtuin 2 (SIRT2), histone deacetylase protein family, plays a central role in the regulation of various pathways. Hence, identification of drug for SIRT2 has attracted great interest in the drug discovery community. To elucidate the molecular basis of the small molecules interactions to inhibit the SIRT2 function we employed the molecular docking, molecular dynamics simulations, and the molecular mechanism Poisson-Boltzmann/ surface area (MM-PBSA) calculations. Five well know inhibitors such as suramin, mol-6, sirtinol, 67, and nf675 were selected to establish the nature of the binding mode of the inhibitors in the SIRT2 active site. The molecular docking and dynamics simulations results revealed that the hydrogen bonds between Arg97 and Gln167 are crucial to inhibit the function of SIRT2. In addition, the MM-PBSA calculations revealed that binding of inhibitors to SIRT2 is mainly driven by van der Waals/non-polar interactions. Although the five inhibitors are very different in structure, shape, and electrostatic potential, they are able to fit in the same binding pocket. These findings from this study provide insights to elucidate the binding pattern of SIRT2 inhibitors and help in the rational structure-based design of novel SIRT2 inhibitors with improved potency and better resistance profile.
- Subjects :
- Protein Conformation
Biophysics
lcsh:Medicine
Molecular Dynamics Simulation
Bioinformatics
Molecular Docking Simulation
Biochemistry
Biophysics Simulations
Molecular dynamics
Structure-Activity Relationship
Protein structure
Computational Chemistry
Sirtuin 2
Catalytic Domain
Drug Discovery
Biochemical Simulations
Humans
Binding site
Biomacromolecule-Ligand Interactions
lcsh:Science
Biochemistry Simulations
Biology
Multidisciplinary
Binding Sites
biology
Chemistry
Drug discovery
lcsh:R
Active site
Proteins
Computational Biology
Hydrogen Bonding
Small molecule
Histone Deacetylase Inhibitors
Docking (molecular)
Small Molecules
biology.protein
Thermodynamics
lcsh:Q
Biophysic Al Simulations
Structural Proteins
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....e19248b0bd11a2a719459057373a4408