Asset Details
Do you wish to reserve the book?
Unveiling of phosphodiesterase-5 hot residues binding to xanthine derivatives for erectile dysfunction therapy: A computational drug repurposing approach
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?
Unveiling of phosphodiesterase-5 hot residues binding to xanthine derivatives for erectile dysfunction therapy: A computational drug repurposing approach
Do you wish to request the book?
Unveiling of phosphodiesterase-5 hot residues binding to xanthine derivatives for erectile dysfunction therapy: A computational drug repurposing approach
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
Unveiling of phosphodiesterase-5 hot residues binding to xanthine derivatives for erectile dysfunction therapy: A computational drug repurposing approach
2025
Overview
Overexpression of phosphodiesterase 5 (PDE-5) presents a compelling target for the therapy of erectile dysfunction. Sildenafil and other conventional PDE-5 inhibitors may lead to adverse effects, including visual disturbances and migraines. Therefore, the investigation of novel inhibitors with enhanced safety profiles is imperative. This research employed a computational drug repurposing approach to assess US-FDA-approved xanthine derivatives (XDs) for their efficacy in targeting PDE-5. XDs exhibit a favorable affinity for the active site of the PDE-5 receptor, with binding scores between −10.0 kcal/mol and −6.3 kcal/mol for linagliptin and theobromine, respectively. The top-ranked docked Xds then underwent 300-nanosecond molecular dynamics simulations. Linagliptin demonstrated greater stability in the binding pocket (RMSD = 1.60 ± 0.34) compared to the typical inhibitor sildenafil (RMSD = 1.70 ± 0.27). The findings were corroborated by MM-PBSA calculation, which showed that linagliptin’s binding free energy of −45.6 ± 4.3 kcal/mol comparable with sildenafil’s −49.0 ± 3.1 kcal/mol. This value is notably higher than that of the deprotonated form of sildenafil, which is present at a 37.06% ratio at physiological pH 7.4. Additionally, we used per-residue energy decomposition to identify crucial residues for PDE-5 activity and thoroughly investigated hydrogen bond occupancy. This study points outthe potential of linagliptin as a PDE-5 inhibitor, paving the way for the development of a safe treatment for erectile dysfunction.
Publisher
Public Library of Science,PLOS,Public Library of Science (PLoS)
Subject
/ Cyclic Nucleotide Phosphodiesterases, Type 5 - chemistry
/ Cyclic Nucleotide Phosphodiesterases, Type 5 - metabolism
/ Energy
/ Erectile Dysfunction - drug therapy
/ Humans
/ Ligands
/ Linagliptin - therapeutic use
/ Lungs
/ Male
/ Medicine and Health Sciences
/ Methods
/ Molecular Docking Simulation
/ Molecular Dynamics Simulation
/ Partial differential equations
/ Phosphodiesterase 5 Inhibitors - chemistry
/ Phosphodiesterase 5 Inhibitors - pharmacology
/ Phosphodiesterase 5 Inhibitors - therapeutic use
/ Proteins
/ Research and Analysis Methods
/ Residues
/ Sildenafil Citrate - chemistry
/ Testing
/ Xanthine
