Binding kinetics of ten small-molecule drug candidates on SARS-CoV-2 3CLpro revealed by biomolecular simulations
3CL protease (3CLpro) is the main protease (Mpro) found in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which cuts the coronavirus polyprotein at eleven conserved sites and is essential for the virus replication. Therefore, 3CLpro has been widely used as a promising drug target. Man...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Medicine in Novel Technology and Devices |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590093523000528 |
| _version_ | 1827615753003597824 |
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| author | Yifei Zhou Xubo Lin |
| author_facet | Yifei Zhou Xubo Lin |
| author_sort | Yifei Zhou |
| collection | DOAJ |
| description | 3CL protease (3CLpro) is the main protease (Mpro) found in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which cuts the coronavirus polyprotein at eleven conserved sites and is essential for the virus replication. Therefore, 3CLpro has been widely used as a promising drug target. Many small-molecule drug candidates targeting 3CLpro have been proposed to inhibit the virus replication. In this work, we aim to reveal detailed interactions between ten small candidate molecules with extensive attention and 3CLpro using molecular docking and molecular dynamics simulations. First, we identified the possible binding sites of these candidate molecules on 3CLpro via molecular docking. Then, a series of 100 ns all-atom molecular dynamics simulations of strongest binding modes were performed to further evaluate the dynamical interactions between the molecules and 3CLpro in detail. Last, the binding free energy of these molecules on 3CLpro was calculated using MM/PBSA calculation, where the contribution of key amino acids was highlighted. The binding kinetics revealed in this work may provide useful insights into the action mechanism and applicability of these small-molecule drug candidates. |
| first_indexed | 2024-03-09T09:16:09Z |
| format | Article |
| id | doaj.art-ce456a74fa424451821fcf2476143a45 |
| institution | Directory Open Access Journal |
| issn | 2590-0935 |
| language | English |
| last_indexed | 2024-03-09T09:16:09Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Medicine in Novel Technology and Devices |
| spelling | doaj.art-ce456a74fa424451821fcf2476143a452023-12-02T07:06:42ZengElsevierMedicine in Novel Technology and Devices2590-09352023-12-0120100257Binding kinetics of ten small-molecule drug candidates on SARS-CoV-2 3CLpro revealed by biomolecular simulationsYifei Zhou0Xubo Lin1Beijing Advanced Innovation Center for Biomedical Engineering, School of Engineering Medicine & School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, ChinaCorresponding author.; Beijing Advanced Innovation Center for Biomedical Engineering, School of Engineering Medicine & School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, China3CL protease (3CLpro) is the main protease (Mpro) found in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which cuts the coronavirus polyprotein at eleven conserved sites and is essential for the virus replication. Therefore, 3CLpro has been widely used as a promising drug target. Many small-molecule drug candidates targeting 3CLpro have been proposed to inhibit the virus replication. In this work, we aim to reveal detailed interactions between ten small candidate molecules with extensive attention and 3CLpro using molecular docking and molecular dynamics simulations. First, we identified the possible binding sites of these candidate molecules on 3CLpro via molecular docking. Then, a series of 100 ns all-atom molecular dynamics simulations of strongest binding modes were performed to further evaluate the dynamical interactions between the molecules and 3CLpro in detail. Last, the binding free energy of these molecules on 3CLpro was calculated using MM/PBSA calculation, where the contribution of key amino acids was highlighted. The binding kinetics revealed in this work may provide useful insights into the action mechanism and applicability of these small-molecule drug candidates.http://www.sciencedirect.com/science/article/pii/S25900935230005283CLproMolecular dockingMD simulationMM/PBSA |
| spellingShingle | Yifei Zhou Xubo Lin Binding kinetics of ten small-molecule drug candidates on SARS-CoV-2 3CLpro revealed by biomolecular simulations Medicine in Novel Technology and Devices 3CLpro Molecular docking MD simulation MM/PBSA |
| title | Binding kinetics of ten small-molecule drug candidates on SARS-CoV-2 3CLpro revealed by biomolecular simulations |
| title_full | Binding kinetics of ten small-molecule drug candidates on SARS-CoV-2 3CLpro revealed by biomolecular simulations |
| title_fullStr | Binding kinetics of ten small-molecule drug candidates on SARS-CoV-2 3CLpro revealed by biomolecular simulations |
| title_full_unstemmed | Binding kinetics of ten small-molecule drug candidates on SARS-CoV-2 3CLpro revealed by biomolecular simulations |
| title_short | Binding kinetics of ten small-molecule drug candidates on SARS-CoV-2 3CLpro revealed by biomolecular simulations |
| title_sort | binding kinetics of ten small molecule drug candidates on sars cov 2 3clpro revealed by biomolecular simulations |
| topic | 3CLpro Molecular docking MD simulation MM/PBSA |
| url | http://www.sciencedirect.com/science/article/pii/S2590093523000528 |
| work_keys_str_mv | AT yifeizhou bindingkineticsoftensmallmoleculedrugcandidatesonsarscov23clprorevealedbybiomolecularsimulations AT xubolin bindingkineticsoftensmallmoleculedrugcandidatesonsarscov23clprorevealedbybiomolecularsimulations |