Docking and Molecular Dynamics Simulations Clarify Binding Sites for Interactions of Novel Marine Sulfated Glycans with SARS-CoV-2 Spike Glycoprotein
The entry of SARS-CoV-2 into the host cell is mediated by its S-glycoprotein (SGP). Sulfated glycans bind to the SGP receptor-binding domain (RBD), which forms a ternary complex with its receptor angiotensin converting enzyme 2. Here, we have conducted a thorough and systematic computational study o...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/17/6413 |
| _version_ | 1797582114523185152 |
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| author | Priyanka Samanta Sushil K. Mishra Vitor H. Pomin Robert J. Doerksen |
| author_facet | Priyanka Samanta Sushil K. Mishra Vitor H. Pomin Robert J. Doerksen |
| author_sort | Priyanka Samanta |
| collection | DOAJ |
| description | The entry of SARS-CoV-2 into the host cell is mediated by its S-glycoprotein (SGP). Sulfated glycans bind to the SGP receptor-binding domain (RBD), which forms a ternary complex with its receptor angiotensin converting enzyme 2. Here, we have conducted a thorough and systematic computational study of the binding of four oligosaccharide building blocks from novel marine sulfated glycans (isolated from <i>Pentacta pygmaea</i> and <i>Isostichopus badionotus</i>) to the non-glycosylated and glycosylated RBD. Blind docking studies using three docking programs identified five potential cryptic binding sites. Extensive site-targeted docking and molecular dynamics simulations using two force fields confirmed only two binding sites (Sites 1 and 5) for these novel, highly charged sulfated glycans, which were also confirmed by previously published reports. This work showed the structural features and key interactions driving ligand binding. A previous study predicted Site 2 to be a potential binding site, which was not observed here. The use of several molecular modeling approaches gave a comprehensive assessment. The detailed comparative study utilizing multiple modeling approaches is the first of its kind for novel glycan–SGP interaction characterization. This study provided insights into the key structural features of these novel glycans as they are considered for development as potential therapeutics. |
| first_indexed | 2024-03-10T23:16:18Z |
| format | Article |
| id | doaj.art-53fb839b30004f16994a806733a3a85e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T23:16:18Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-53fb839b30004f16994a806733a3a85e2023-11-19T08:35:40ZengMDPI AGMolecules1420-30492023-09-012817641310.3390/molecules28176413Docking and Molecular Dynamics Simulations Clarify Binding Sites for Interactions of Novel Marine Sulfated Glycans with SARS-CoV-2 Spike GlycoproteinPriyanka Samanta0Sushil K. Mishra1Vitor H. Pomin2Robert J. Doerksen3Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677-1848, USADepartment of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677-1848, USADepartment of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677-1848, USADepartment of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677-1848, USAThe entry of SARS-CoV-2 into the host cell is mediated by its S-glycoprotein (SGP). Sulfated glycans bind to the SGP receptor-binding domain (RBD), which forms a ternary complex with its receptor angiotensin converting enzyme 2. Here, we have conducted a thorough and systematic computational study of the binding of four oligosaccharide building blocks from novel marine sulfated glycans (isolated from <i>Pentacta pygmaea</i> and <i>Isostichopus badionotus</i>) to the non-glycosylated and glycosylated RBD. Blind docking studies using three docking programs identified five potential cryptic binding sites. Extensive site-targeted docking and molecular dynamics simulations using two force fields confirmed only two binding sites (Sites 1 and 5) for these novel, highly charged sulfated glycans, which were also confirmed by previously published reports. This work showed the structural features and key interactions driving ligand binding. A previous study predicted Site 2 to be a potential binding site, which was not observed here. The use of several molecular modeling approaches gave a comprehensive assessment. The detailed comparative study utilizing multiple modeling approaches is the first of its kind for novel glycan–SGP interaction characterization. This study provided insights into the key structural features of these novel glycans as they are considered for development as potential therapeutics.https://www.mdpi.com/1420-3049/28/17/6413cryptic binding sitesglycosaminoglycansmolecular dockingmolecular dynamicsbinding free energySARS-CoV-2 spike glycoprotein |
| spellingShingle | Priyanka Samanta Sushil K. Mishra Vitor H. Pomin Robert J. Doerksen Docking and Molecular Dynamics Simulations Clarify Binding Sites for Interactions of Novel Marine Sulfated Glycans with SARS-CoV-2 Spike Glycoprotein Molecules cryptic binding sites glycosaminoglycans molecular docking molecular dynamics binding free energy SARS-CoV-2 spike glycoprotein |
| title | Docking and Molecular Dynamics Simulations Clarify Binding Sites for Interactions of Novel Marine Sulfated Glycans with SARS-CoV-2 Spike Glycoprotein |
| title_full | Docking and Molecular Dynamics Simulations Clarify Binding Sites for Interactions of Novel Marine Sulfated Glycans with SARS-CoV-2 Spike Glycoprotein |
| title_fullStr | Docking and Molecular Dynamics Simulations Clarify Binding Sites for Interactions of Novel Marine Sulfated Glycans with SARS-CoV-2 Spike Glycoprotein |
| title_full_unstemmed | Docking and Molecular Dynamics Simulations Clarify Binding Sites for Interactions of Novel Marine Sulfated Glycans with SARS-CoV-2 Spike Glycoprotein |
| title_short | Docking and Molecular Dynamics Simulations Clarify Binding Sites for Interactions of Novel Marine Sulfated Glycans with SARS-CoV-2 Spike Glycoprotein |
| title_sort | docking and molecular dynamics simulations clarify binding sites for interactions of novel marine sulfated glycans with sars cov 2 spike glycoprotein |
| topic | cryptic binding sites glycosaminoglycans molecular docking molecular dynamics binding free energy SARS-CoV-2 spike glycoprotein |
| url | https://www.mdpi.com/1420-3049/28/17/6413 |
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