Identification of potential modulators for human GPD1 by docking-based virtual screening, molecular dynamics simulations, binding free energy calculations, and DeLA-drug analysis.
Binding free energy calculations
GPD1
Molecular docking
Molecular dynamics simulation
Virtual screening
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 06 2024
19 06 2024
Historique:
received:
10
07
2023
accepted:
06
05
2024
medline:
20
6
2024
pubmed:
20
6
2024
entrez:
19
6
2024
Statut:
epublish
Résumé
Cytosolic Glycerol-3-phosphate dehydrogenase 1 (GPD1, EC 1.1.1.8) plays a pivotal role in regulating the Embden-Meyerhof glucose glycolysis pathway (E-M pathway), as well as in conditions such as Huntington's disease, cancer, and its potential role as a specific marker for Dormant Glioma Stem Cells. In this study, we conducted virtual screening using the ZINC database ( http://zinc.docking.org/ ) and the GPD1 structure to identify potential GPD1 modulators. The investigation involved screening active candidate ligands using ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) parameters, combined with molecular docking, pose analysis, and interaction analysis based on Lipinski and Veber criteria. Subsequently, the top 10 ligands were subjected to 200 ns all-atom molecular dynamics (M.D.) simulations, and binding free energies were calculated. The findings revealed that specific residues, namely TRP14, PRO94, LYS120, ASN151, THR264, ASP260, and GLN298, played a crucial role in ensuring system stability. Furthermore, through a comprehensive analysis involving molecular docking, molecular M.D., and DeLA-Drug, we identified 10 promising small molecules. These molecules represent potential lead compounds for developing effective therapeutics targeting GPD1-associated diseases, thereby contributing to a deeper understanding of GPD1-associated mechanisms. This study's significance lies in identifying key residues associated with GPD1 and discovering valuable small molecules, providing a foundation for further research and development.
Identifiants
pubmed: 38898093
doi: 10.1038/s41598-024-61439-y
pii: 10.1038/s41598-024-61439-y
doi:
Substances chimiques
Ligands
0
Glycerolphosphate Dehydrogenase
EC 1.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
14123Subventions
Organisme : National key research and development program of China
ID : 2018YFA0108304
Organisme : College Student Innovation and Entrepreneurship Training Program of Guangxi University
ID : 202210593534
Informations de copyright
© 2024. The Author(s).
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