Natural compound targeting BDNF V66M variant: insights from in silico docking and molecular analysis
Abstract Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin gene family gene that encodes proteins vital for the growth, maintenance, and survival of neurons in the nervous system. The study aimed to screen natural compounds against BDNF variant (V66M), which affects memory, cognition, and m...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2023-11-01
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| Series: | AMB Express |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13568-023-01640-w |
| _version_ | 1797413846046998528 |
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| author | Azra Sakhawat Muhammad Umer Khan Raima Rehman Samiullah Khan Muhammad Adnan Shan Alia Batool Muhammad Arshad Javed Qurban Ali |
| author_facet | Azra Sakhawat Muhammad Umer Khan Raima Rehman Samiullah Khan Muhammad Adnan Shan Alia Batool Muhammad Arshad Javed Qurban Ali |
| author_sort | Azra Sakhawat |
| collection | DOAJ |
| description | Abstract Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin gene family gene that encodes proteins vital for the growth, maintenance, and survival of neurons in the nervous system. The study aimed to screen natural compounds against BDNF variant (V66M), which affects memory, cognition, and mood regulation. BDNF variant (V66M) as a target structure was selected, and Vitamin D, Curcumin, Vitamin C, and Quercetin as ligands structures were taken from PubChem database. Multiple tools like AUTODOCK VINA, BIOVIA discovery studio, PyMOL, CB-dock, IMOD server, Swiss ADEMT, and Swiss predict ligands target were used to analyze binding energy, interaction, stability, toxicity, and visualize BDNF-ligand complexes. Compounds Vitamin D3, Curcumin, Vitamin C, and Quercetin with binding energies values of − 5.5, − 6.1, − 4.5, and − 6.7 kj/mol, respectively, were selected. The ligands bind to the active sites of the BDNF variant (V66M) via hydrophobic bonds, hydrogen bonds, and electrostatic interactions. Furthermore, ADMET analysis of the ligands revealed they exhibited sound pharmacokinetic and toxicity profiles. In addition, an MD simulation study showed that the most active ligand bound favorably and dynamically to the target protein, and protein–ligand complex stability was determined. The finding of this research could provide an excellent platform for discovering and rationalizing novel drugs against stress related to BDNF (V66M). Docking, preclinical drug testing and MD simulation results suggest Quercetin as a more potent BDNF variant (V66M) inhibitor and forming a more structurally stable complex. |
| first_indexed | 2024-03-09T05:24:55Z |
| format | Article |
| id | doaj.art-0b8a19963bdf43d69eb2e45374598b84 |
| institution | Directory Open Access Journal |
| issn | 2191-0855 |
| language | English |
| last_indexed | 2024-03-09T05:24:55Z |
| publishDate | 2023-11-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | AMB Express |
| spelling | doaj.art-0b8a19963bdf43d69eb2e45374598b842023-12-03T12:37:22ZengSpringerOpenAMB Express2191-08552023-11-0113111610.1186/s13568-023-01640-wNatural compound targeting BDNF V66M variant: insights from in silico docking and molecular analysisAzra Sakhawat0Muhammad Umer Khan1Raima Rehman2Samiullah Khan3Muhammad Adnan Shan4Alia Batool5Muhammad Arshad Javed6Qurban Ali7Institute of Molecular Biology and Biotechnology, The University of LahoreInstitute of Molecular Biology and Biotechnology, The University of LahoreInstitute of Molecular Biology and Biotechnology, The University of LahoreInstitute of Molecular Biology and Biotechnology, The University of LahoreCentre for Applied Molecular Biology, University of the PunjabDepartment of Plant Breeding and Genetics, Faculty of Agricultural Sciences, University of the PunjabDepartment of Plant Breeding and Genetics, Faculty of Agricultural Sciences, University of the PunjabDepartment of Plant Breeding and Genetics, Faculty of Agricultural Sciences, University of the PunjabAbstract Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin gene family gene that encodes proteins vital for the growth, maintenance, and survival of neurons in the nervous system. The study aimed to screen natural compounds against BDNF variant (V66M), which affects memory, cognition, and mood regulation. BDNF variant (V66M) as a target structure was selected, and Vitamin D, Curcumin, Vitamin C, and Quercetin as ligands structures were taken from PubChem database. Multiple tools like AUTODOCK VINA, BIOVIA discovery studio, PyMOL, CB-dock, IMOD server, Swiss ADEMT, and Swiss predict ligands target were used to analyze binding energy, interaction, stability, toxicity, and visualize BDNF-ligand complexes. Compounds Vitamin D3, Curcumin, Vitamin C, and Quercetin with binding energies values of − 5.5, − 6.1, − 4.5, and − 6.7 kj/mol, respectively, were selected. The ligands bind to the active sites of the BDNF variant (V66M) via hydrophobic bonds, hydrogen bonds, and electrostatic interactions. Furthermore, ADMET analysis of the ligands revealed they exhibited sound pharmacokinetic and toxicity profiles. In addition, an MD simulation study showed that the most active ligand bound favorably and dynamically to the target protein, and protein–ligand complex stability was determined. The finding of this research could provide an excellent platform for discovering and rationalizing novel drugs against stress related to BDNF (V66M). Docking, preclinical drug testing and MD simulation results suggest Quercetin as a more potent BDNF variant (V66M) inhibitor and forming a more structurally stable complex.https://doi.org/10.1186/s13568-023-01640-wBrain derived neurotropic factorTherapyValineMethionine |
| spellingShingle | Azra Sakhawat Muhammad Umer Khan Raima Rehman Samiullah Khan Muhammad Adnan Shan Alia Batool Muhammad Arshad Javed Qurban Ali Natural compound targeting BDNF V66M variant: insights from in silico docking and molecular analysis AMB Express Brain derived neurotropic factor Therapy Valine Methionine |
| title | Natural compound targeting BDNF V66M variant: insights from in silico docking and molecular analysis |
| title_full | Natural compound targeting BDNF V66M variant: insights from in silico docking and molecular analysis |
| title_fullStr | Natural compound targeting BDNF V66M variant: insights from in silico docking and molecular analysis |
| title_full_unstemmed | Natural compound targeting BDNF V66M variant: insights from in silico docking and molecular analysis |
| title_short | Natural compound targeting BDNF V66M variant: insights from in silico docking and molecular analysis |
| title_sort | natural compound targeting bdnf v66m variant insights from in silico docking and molecular analysis |
| topic | Brain derived neurotropic factor Therapy Valine Methionine |
| url | https://doi.org/10.1186/s13568-023-01640-w |
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