Asset Details
Do you wish to reserve the book?
In silico identification of novel ligands targeting stress-related human FKBP5 protein in mental disorders
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?
In silico identification of novel ligands targeting stress-related human FKBP5 protein in mental disorders
Do you wish to request the book?
In silico identification of novel ligands targeting stress-related human FKBP5 protein in mental disorders
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
In silico identification of novel ligands targeting stress-related human FKBP5 protein in mental disorders
2025
Overview
FK506-binding protein 51 (FKBP51 or FKBP5) serves as a crucial stress modulator implicated in mental disorders, presenting a potential target for intervention. Inhibitors like SAFit2, rapamycin, and tacrolimus exhibit promising interactions with this protein. Despite these advances, challenges persist in diversifying FKBP5 ligands, prompting further exploration of interaction partners. Hence, this study aims to identify other potential ligands. Employing molecular docking, we generated complexes with various ligands (rapamycin, tacrolimus, SAFit2-Selective antagonist of FKBP51 by induced fit, ascomycin, pimecrolimus, rosavin, salidroside, curcumin, apigenin, uvaricin, ruscogenin, neoruscogenin, pumicalagin, castalagin, and grandinin). We identified the top 3 best ligands, of which ruscogenin and neoruscogenin had notable abilities to cross the blood-brain barrier and have high gastrointestinal absorption, like curcumin. Toxicity predictions show ruscogenin and neoruscogenin to be the least toxic based on oral toxicity classification (Class VI). Tyrosine (Tyr113) formed consistent interactions with all ligands in the complex, reinforcing their potential and involvement in stress modulation. Molecular dynamic (MD) simulation validated strong interactions between our three key ligands and FKBP5 protein and provided an understanding of the stability of the complex. The binding free energy (ΔG) of the best ligands (based on pharmacological properties) from MD simulation analysis is -31.78 kcal/mol for neoruscogenin, -30.41 kcal/mol for ruscogenin, and -27.6 kcal/mol for curcumin. These molecules, therefore, can serve as therapeutic molecules or biomarkers for research in stress-impacted mental disorders. While offering therapeutic implications for mental disorders by attenuating stress impact, it is crucial to emphasize that these ligands’ transition to clinical applications necessitates extensive experimental research, including clinical trials, to unravel the intricate molecular and neural pathways involved in these interactions.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Curcumin
/ Humans
/ Ligands
/ Medicine and Health Sciences
/ Mental Disorders - drug therapy
/ Mental Disorders - metabolism
/ Molecular Docking Simulation
/ Molecular Dynamics Simulation
/ Proteins
/ Tacrolimus Binding Proteins - antagonists & inhibitors
/ Tacrolimus Binding Proteins - chemistry
/ Tacrolimus Binding Proteins - metabolism
/ Toxicity
/ Tyrosine
We currently cannot retrieve any items related to this title. Kindly check back at a later time.