Computational Prediction of Hot Spots and Binding Site of Inhibitor NSC23766 on Rac1 Binding With Tiam1
Rac1 is a small signaling protein, which belongs to the Rho subfamily of Ras superfamily. It is activated by binding GTP and inactivated by exchanging GDP for GTP. The ability of nucleotide exchange depends on guanine nucleotide exchange factors (GEFs) family proteins. T-lymphoma invasion and metast...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-02-01
|
| Series: | Frontiers in Chemistry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2020.625437/full |
| _version_ | 1818578929307353088 |
|---|---|
| author | Chunwen Zheng Xiaodong Wu Xiaodong Wu Ruijie Zeng Lirui Lin Lirui Lin Liyan Xu Enmin Li Enmin Li Geng Dong Geng Dong |
| author_facet | Chunwen Zheng Xiaodong Wu Xiaodong Wu Ruijie Zeng Lirui Lin Lirui Lin Liyan Xu Enmin Li Enmin Li Geng Dong Geng Dong |
| author_sort | Chunwen Zheng |
| collection | DOAJ |
| description | Rac1 is a small signaling protein, which belongs to the Rho subfamily of Ras superfamily. It is activated by binding GTP and inactivated by exchanging GDP for GTP. The ability of nucleotide exchange depends on guanine nucleotide exchange factors (GEFs) family proteins. T-lymphoma invasion and metastasis factor 1 (Tiam1) is a member of GEFs. Rac1 participates in multiple signaling pathways and regulates various cellular events by interacting with GEFs. Particularly, it is involved in the development and progression of various kinds of tumors. In this paper, we have studied the detailed interaction between Rac1 and Tiam1. Seven residues on Rac1 are predicted to be important for the interaction with Tiam1, i.e. E31, Y32, D38, N39, Y64, D65 and W56. All these residues are located on the switch 1 and 2 domains which are the interface between Rac1 and Tiam1, except W56. In addition, we analyzed how inhibitor NSC23766 interacts with Rac1. Our docking results show that NSC23766 binds to the same region as Tiam1. Several residues, i.e. F37, D38, N39, W56, Y64, L67, L70 and S71, contribute much to binding free energy. These findings are very useful for the structure-based design of inhibitors toward Rac1. |
| first_indexed | 2024-12-16T06:53:37Z |
| format | Article |
| id | doaj.art-446a6ebd09e14ef58cea90626d6bf61f |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-16T06:53:37Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-446a6ebd09e14ef58cea90626d6bf61f2022-12-21T22:40:20ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462021-02-01810.3389/fchem.2020.625437625437Computational Prediction of Hot Spots and Binding Site of Inhibitor NSC23766 on Rac1 Binding With Tiam1Chunwen Zheng0Xiaodong Wu1Xiaodong Wu2Ruijie Zeng3Lirui Lin4Lirui Lin5Liyan Xu6Enmin Li7Enmin Li8Geng Dong9Geng Dong10Shantou University Medical College, Shantou, ChinaDepartment of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, ChinaMedical Informatics Research Center, Shantou University Medical College, Shantou, ChinaShantou University Medical College, Shantou, ChinaDepartment of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, ChinaMedical Informatics Research Center, Shantou University Medical College, Shantou, ChinaKey Laboratory of Molecular Biology in High Cancer Incidence Coastal Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, ChinaDepartment of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, ChinaKey Laboratory of Molecular Biology in High Cancer Incidence Coastal Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, ChinaDepartment of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, ChinaMedical Informatics Research Center, Shantou University Medical College, Shantou, ChinaRac1 is a small signaling protein, which belongs to the Rho subfamily of Ras superfamily. It is activated by binding GTP and inactivated by exchanging GDP for GTP. The ability of nucleotide exchange depends on guanine nucleotide exchange factors (GEFs) family proteins. T-lymphoma invasion and metastasis factor 1 (Tiam1) is a member of GEFs. Rac1 participates in multiple signaling pathways and regulates various cellular events by interacting with GEFs. Particularly, it is involved in the development and progression of various kinds of tumors. In this paper, we have studied the detailed interaction between Rac1 and Tiam1. Seven residues on Rac1 are predicted to be important for the interaction with Tiam1, i.e. E31, Y32, D38, N39, Y64, D65 and W56. All these residues are located on the switch 1 and 2 domains which are the interface between Rac1 and Tiam1, except W56. In addition, we analyzed how inhibitor NSC23766 interacts with Rac1. Our docking results show that NSC23766 binds to the same region as Tiam1. Several residues, i.e. F37, D38, N39, W56, Y64, L67, L70 and S71, contribute much to binding free energy. These findings are very useful for the structure-based design of inhibitors toward Rac1.https://www.frontiersin.org/articles/10.3389/fchem.2020.625437/fullRac1Tiam1NSC23766molecular dockingMD simulationbinding free energy |
| spellingShingle | Chunwen Zheng Xiaodong Wu Xiaodong Wu Ruijie Zeng Lirui Lin Lirui Lin Liyan Xu Enmin Li Enmin Li Geng Dong Geng Dong Computational Prediction of Hot Spots and Binding Site of Inhibitor NSC23766 on Rac1 Binding With Tiam1 Frontiers in Chemistry Rac1 Tiam1 NSC23766 molecular docking MD simulation binding free energy |
| title | Computational Prediction of Hot Spots and Binding Site of Inhibitor NSC23766 on Rac1 Binding With Tiam1 |
| title_full | Computational Prediction of Hot Spots and Binding Site of Inhibitor NSC23766 on Rac1 Binding With Tiam1 |
| title_fullStr | Computational Prediction of Hot Spots and Binding Site of Inhibitor NSC23766 on Rac1 Binding With Tiam1 |
| title_full_unstemmed | Computational Prediction of Hot Spots and Binding Site of Inhibitor NSC23766 on Rac1 Binding With Tiam1 |
| title_short | Computational Prediction of Hot Spots and Binding Site of Inhibitor NSC23766 on Rac1 Binding With Tiam1 |
| title_sort | computational prediction of hot spots and binding site of inhibitor nsc23766 on rac1 binding with tiam1 |
| topic | Rac1 Tiam1 NSC23766 molecular docking MD simulation binding free energy |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2020.625437/full |
| work_keys_str_mv | AT chunwenzheng computationalpredictionofhotspotsandbindingsiteofinhibitornsc23766onrac1bindingwithtiam1 AT xiaodongwu computationalpredictionofhotspotsandbindingsiteofinhibitornsc23766onrac1bindingwithtiam1 AT xiaodongwu computationalpredictionofhotspotsandbindingsiteofinhibitornsc23766onrac1bindingwithtiam1 AT ruijiezeng computationalpredictionofhotspotsandbindingsiteofinhibitornsc23766onrac1bindingwithtiam1 AT liruilin computationalpredictionofhotspotsandbindingsiteofinhibitornsc23766onrac1bindingwithtiam1 AT liruilin computationalpredictionofhotspotsandbindingsiteofinhibitornsc23766onrac1bindingwithtiam1 AT liyanxu computationalpredictionofhotspotsandbindingsiteofinhibitornsc23766onrac1bindingwithtiam1 AT enminli computationalpredictionofhotspotsandbindingsiteofinhibitornsc23766onrac1bindingwithtiam1 AT enminli computationalpredictionofhotspotsandbindingsiteofinhibitornsc23766onrac1bindingwithtiam1 AT gengdong computationalpredictionofhotspotsandbindingsiteofinhibitornsc23766onrac1bindingwithtiam1 AT gengdong computationalpredictionofhotspotsandbindingsiteofinhibitornsc23766onrac1bindingwithtiam1 |