Asset Details
Do you wish to reserve the book?
A Combined Computational and Experimental Approach to Studying Tropomyosin Kinase Receptor B Binders for Potential Treatment of Neurodegenerative Diseases
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
A Combined Computational and Experimental Approach to Studying Tropomyosin Kinase Receptor B Binders for Potential Treatment of Neurodegenerative Diseases
Do you wish to request the book?
A Combined Computational and Experimental Approach to Studying Tropomyosin Kinase Receptor B Binders for Potential Treatment of Neurodegenerative Diseases
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
A Combined Computational and Experimental Approach to Studying Tropomyosin Kinase Receptor B Binders for Potential Treatment of Neurodegenerative Diseases
2024
Overview
Tropomyosin kinase receptor B (TrkB) has been explored as a therapeutic target for neurological and psychiatric disorders. However, the development of TrkB agonists was hindered by our poor understanding of the TrkB agonist binding location and affinity (both affect the regulation of disorder types). This motivated us to develop a combined computational and experimental approach to study TrkB binders. First, we developed a docking method to simulate the binding affinity of TrkB and binders identified by our magnetic drug screening platform from Gotu kola extracts. The Fred Docking scores from the docking computation showed strong agreement with the experimental results. Subsequently, using this screening platform, we identified a list of compounds from the NIH clinical collection library and applied the same docking studies. From the Fred Docking scores, we selected two compounds for TrkB activation tests. Interestingly, the ability of the compounds to increase dendritic arborization in hippocampal neurons matched well with the computational results. Finally, we performed a detailed binding analysis of the top candidates and compared them with the best-characterized TrkB agonist, 7,8-dyhydroxyflavon. The screening platform directly identifies TrkB binders, and the computational approach allows for the quick selection of top candidates with potential biological activities based on the docking scores.
Publisher
MDPI AG
Subject
/ Brain-derived neurotrophic factor
/ Disease
/ Humans
/ Kinases
/ Ligands
/ Membrane Glycoproteins - chemistry
/ Membrane Glycoproteins - genetics
/ Membrane Glycoproteins - metabolism
/ Molecular Docking Simulation
/ Neurodegenerative Diseases - drug therapy
/ Neurodegenerative Diseases - genetics
/ Neurodegenerative Diseases - metabolism
/ Neurons
/ Protein Structure, Quaternary
/ Proteins
