Identification of Inhibitor Binding Site in Human Sirtuin 2 Using Molecular Docking and Dynamics Simulations
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...
| Main Authors: | , , , , |
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| Format: | Journal Article |
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PLOS
2013
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| Online Access: | http://hdl.handle.net/20.500.11937/33925 |
| _version_ | 1848754081193000960 |
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| author | Sakkiah, Sugunadevi Arooj, Mahreen Rajesh Kumar, Manian Hyun Eom, Soo Woo Lee, Keun |
| author_facet | Sakkiah, Sugunadevi Arooj, Mahreen Rajesh Kumar, Manian Hyun Eom, Soo Woo Lee, Keun |
| author_sort | Sakkiah, Sugunadevi |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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 bindingpocket. 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. |
| first_indexed | 2025-11-14T08:34:44Z |
| format | Journal Article |
| id | curtin-20.500.11937-33925 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:34:44Z |
| publishDate | 2013 |
| publisher | PLOS |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-339252017-09-13T15:07:14Z Identification of Inhibitor Binding Site in Human Sirtuin 2 Using Molecular Docking and Dynamics Simulations Sakkiah, Sugunadevi Arooj, Mahreen Rajesh Kumar, Manian Hyun Eom, Soo Woo Lee, Keun 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 bindingpocket. 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. 2013 Journal Article http://hdl.handle.net/20.500.11937/33925 10.1371/journal.pone.0051429 PLOS fulltext |
| spellingShingle | Sakkiah, Sugunadevi Arooj, Mahreen Rajesh Kumar, Manian Hyun Eom, Soo Woo Lee, Keun Identification of Inhibitor Binding Site in Human Sirtuin 2 Using Molecular Docking and Dynamics Simulations |
| title | Identification of Inhibitor Binding Site in Human Sirtuin 2 Using Molecular Docking and Dynamics Simulations |
| title_full | Identification of Inhibitor Binding Site in Human Sirtuin 2 Using Molecular Docking and Dynamics Simulations |
| title_fullStr | Identification of Inhibitor Binding Site in Human Sirtuin 2 Using Molecular Docking and Dynamics Simulations |
| title_full_unstemmed | Identification of Inhibitor Binding Site in Human Sirtuin 2 Using Molecular Docking and Dynamics Simulations |
| title_short | Identification of Inhibitor Binding Site in Human Sirtuin 2 Using Molecular Docking and Dynamics Simulations |
| title_sort | identification of inhibitor binding site in human sirtuin 2 using molecular docking and dynamics simulations |
| url | http://hdl.handle.net/20.500.11937/33925 |