A comparative molecular dynamic simulation study on potent ligands targeting mTOR/FRB domain for breast cancer therapy.
FRB domain
PI3K/AKT/mTOR pathway
breast cancer
inhibitors
structure-based drug designing
Journal
Biotechnology and applied biochemistry
ISSN: 1470-8744
Titre abrégé: Biotechnol Appl Biochem
Pays: United States
ID NLM: 8609465
Informations de publication
Date de publication:
Aug 2022
Aug 2022
Historique:
received:
08
02
2021
accepted:
19
05
2021
pubmed:
1
6
2021
medline:
30
8
2022
entrez:
31
5
2021
Statut:
ppublish
Résumé
Our study aimed to develop and find out the best drug candidate against the mechanistic target of rapamycin (mTOR/FRB) domain having a critical role in the aetiology of breast cancer. The FKBP12-rapamycin-binding (FRB) domain in the essential phosphoinositide 3 kinase/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway has been a vital player in the disease progression in breast cancer. By using structure-based drug designing , the best possible targets have been identified and developed. The three-dimensional structure of the target protein was generated using I-TASSER. The ligands were generated against the most suitable target active site using standard tools for active site identification. Furthermore, the seed molecule was drawn using Chemsketch, which was then grown into the pocket using Ligbuilder. The obtained ligands were further validated using online programs for bioavailability and toxicity, followed by molecular dynamic simulations. The study concludes that the equilibrated NVT-NPT complexes indicate LIG2 stability over LIG3. RMSD and RMSF have shown that the complex of LIG2 is more stable than LIG3. LIG2 has the potential antagonistic properties to target the mTOR/FRB domain and has therapeutic implications for breast cancer.
Substances chimiques
Ligands
0
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1339-1347Informations de copyright
© 2021 International Union of Biochemistry and Molecular Biology, Inc.
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