Molecular Docking and Dynamic Simulation of AZD3293 and Solanezumab Effects Against BACE1 to Treat Alzheimer's Disease
The design of novel inhibitors to target BACE1 with reduced cytotoxicity effects is a promising approach to treat Alzheimer's disease (AD). Multiple clinical drugs and antibodies such as AZD3293 and Solanezumab are being tested to investigate their therapeutical potential against AD. The curren...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-06-01
|
| Series: | Frontiers in Computational Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fncom.2018.00034/full |
| _version_ | 1818554402924920832 |
|---|---|
| author | Mubashir Hassan Saba Shahzadi Saba Shahzadi Sung Y. Seo Hany Alashwal Nazar Zaki Ahmed A. Moustafa |
| author_facet | Mubashir Hassan Saba Shahzadi Saba Shahzadi Sung Y. Seo Hany Alashwal Nazar Zaki Ahmed A. Moustafa |
| author_sort | Mubashir Hassan |
| collection | DOAJ |
| description | The design of novel inhibitors to target BACE1 with reduced cytotoxicity effects is a promising approach to treat Alzheimer's disease (AD). Multiple clinical drugs and antibodies such as AZD3293 and Solanezumab are being tested to investigate their therapeutical potential against AD. The current study explores the binding pattern of AZD3293 and Solanezumab against their target proteins such as β-secretase (BACE1) and mid-region amyloid-beta (Aβ) (PDBIDs: 2ZHV & 4XXD), respectively using molecular docking and dynamic simulation (MD) approaches. The molecular docking results show that AZD3293 binds within the active region of BACE1 by forming hydrogen bonds against Asp32 and Lys107 with distances 2.95 and 2.68 Å, respectively. However, the heavy chain of Solanezumab interacts with Lys16 and Asp23 of amyloid beta having bond length 2.82, 2.78, and 3.00 Å, respectively. The dynamic cross correlations and normal mode analyses show that BACE1 depicted good residual correlated motions and fluctuations, as compared to Solanezumab. Using MD, the Root Mean Square Deviation and Fluctuation (RMSD/F) graphs show that AZD3293 residual fluctuations and RMSD value (0.2 nm) was much better compared to Solanezumab (0.7 nm). Moreover, the radius of gyration (Rg) results also depicts the significance of AZD3293 docked complex compared to Solanezumab through residual compactness. Our comparative results show that AZD3293 is a better therapeutic agent for treating AD than Solanezumab. |
| first_indexed | 2024-12-12T09:39:02Z |
| format | Article |
| id | doaj.art-c2a0798d76314d40935052a51b2b2a09 |
| institution | Directory Open Access Journal |
| issn | 1662-5188 |
| language | English |
| last_indexed | 2024-12-12T09:39:02Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Computational Neuroscience |
| spelling | doaj.art-c2a0798d76314d40935052a51b2b2a092022-12-22T00:28:38ZengFrontiers Media S.A.Frontiers in Computational Neuroscience1662-51882018-06-011210.3389/fncom.2018.00034330017Molecular Docking and Dynamic Simulation of AZD3293 and Solanezumab Effects Against BACE1 to Treat Alzheimer's DiseaseMubashir Hassan0Saba Shahzadi1Saba Shahzadi2Sung Y. Seo3Hany Alashwal4Nazar Zaki5Ahmed A. Moustafa6College of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, South KoreaInstitute of Molecular Science and Bioinformatics, Lahore, PakistanDepartment of Bioinformatics, Virtual University Davis Road, Lahore, PakistanCollege of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, South KoreaCollege of Information Technology, United Arab Emirates University, Al-Ain, United Arab EmiratesCollege of Information Technology, United Arab Emirates University, Al-Ain, United Arab EmiratesSchool of Social Sciences and Psychology, MARCS Institute for Brain and Behaviour, Western Sydney University, Sydney, NSW, AustraliaThe design of novel inhibitors to target BACE1 with reduced cytotoxicity effects is a promising approach to treat Alzheimer's disease (AD). Multiple clinical drugs and antibodies such as AZD3293 and Solanezumab are being tested to investigate their therapeutical potential against AD. The current study explores the binding pattern of AZD3293 and Solanezumab against their target proteins such as β-secretase (BACE1) and mid-region amyloid-beta (Aβ) (PDBIDs: 2ZHV & 4XXD), respectively using molecular docking and dynamic simulation (MD) approaches. The molecular docking results show that AZD3293 binds within the active region of BACE1 by forming hydrogen bonds against Asp32 and Lys107 with distances 2.95 and 2.68 Å, respectively. However, the heavy chain of Solanezumab interacts with Lys16 and Asp23 of amyloid beta having bond length 2.82, 2.78, and 3.00 Å, respectively. The dynamic cross correlations and normal mode analyses show that BACE1 depicted good residual correlated motions and fluctuations, as compared to Solanezumab. Using MD, the Root Mean Square Deviation and Fluctuation (RMSD/F) graphs show that AZD3293 residual fluctuations and RMSD value (0.2 nm) was much better compared to Solanezumab (0.7 nm). Moreover, the radius of gyration (Rg) results also depicts the significance of AZD3293 docked complex compared to Solanezumab through residual compactness. Our comparative results show that AZD3293 is a better therapeutic agent for treating AD than Solanezumab.https://www.frontiersin.org/article/10.3389/fncom.2018.00034/fullAlzheimer's diseasecomputational modelingdynamic simulationAZD3293solanezumab |
| spellingShingle | Mubashir Hassan Saba Shahzadi Saba Shahzadi Sung Y. Seo Hany Alashwal Nazar Zaki Ahmed A. Moustafa Molecular Docking and Dynamic Simulation of AZD3293 and Solanezumab Effects Against BACE1 to Treat Alzheimer's Disease Frontiers in Computational Neuroscience Alzheimer's disease computational modeling dynamic simulation AZD3293 solanezumab |
| title | Molecular Docking and Dynamic Simulation of AZD3293 and Solanezumab Effects Against BACE1 to Treat Alzheimer's Disease |
| title_full | Molecular Docking and Dynamic Simulation of AZD3293 and Solanezumab Effects Against BACE1 to Treat Alzheimer's Disease |
| title_fullStr | Molecular Docking and Dynamic Simulation of AZD3293 and Solanezumab Effects Against BACE1 to Treat Alzheimer's Disease |
| title_full_unstemmed | Molecular Docking and Dynamic Simulation of AZD3293 and Solanezumab Effects Against BACE1 to Treat Alzheimer's Disease |
| title_short | Molecular Docking and Dynamic Simulation of AZD3293 and Solanezumab Effects Against BACE1 to Treat Alzheimer's Disease |
| title_sort | molecular docking and dynamic simulation of azd3293 and solanezumab effects against bace1 to treat alzheimer s disease |
| topic | Alzheimer's disease computational modeling dynamic simulation AZD3293 solanezumab |
| url | https://www.frontiersin.org/article/10.3389/fncom.2018.00034/full |
| work_keys_str_mv | AT mubashirhassan moleculardockinganddynamicsimulationofazd3293andsolanezumabeffectsagainstbace1totreatalzheimersdisease AT sabashahzadi moleculardockinganddynamicsimulationofazd3293andsolanezumabeffectsagainstbace1totreatalzheimersdisease AT sabashahzadi moleculardockinganddynamicsimulationofazd3293andsolanezumabeffectsagainstbace1totreatalzheimersdisease AT sungyseo moleculardockinganddynamicsimulationofazd3293andsolanezumabeffectsagainstbace1totreatalzheimersdisease AT hanyalashwal moleculardockinganddynamicsimulationofazd3293andsolanezumabeffectsagainstbace1totreatalzheimersdisease AT nazarzaki moleculardockinganddynamicsimulationofazd3293andsolanezumabeffectsagainstbace1totreatalzheimersdisease AT ahmedamoustafa moleculardockinganddynamicsimulationofazd3293andsolanezumabeffectsagainstbace1totreatalzheimersdisease |