Article ; Online: Ensemble-based virtual screening of African natural products to target human thymidylate synthase.
Journal of molecular graphics & modelling
2023 Volume 125, Page(s) 108568
Abstract: Human thymidylate synthase (hTS) is a validated drug target for chemotherapy. A virtual screening experiment was used to prioritize a list of compounds from African Natural Products Databases docked against the orthosteric binding pocket of hTS. ... ...
Abstract | Human thymidylate synthase (hTS) is a validated drug target for chemotherapy. A virtual screening experiment was used to prioritize a list of compounds from African Natural Products Databases docked against the orthosteric binding pocket of hTS. Consensus scores of binding affinities from ensemble-based virtual screening, hydrated docking and MM-PBSA calculations ranked compounds NEA4433 and NEA4434 as the best candidates owing to binding affinity scores in the picomolar order, their excellent ADMET profiles and the good stability of the protein-ligand complexes formed. The current study demonstrates the role of water in small molecule binding to hTS in mediating protein-ligand interactions. Similarly, the robust ensemble docking (relaxed scheme complex) ranked NEA4433 and NEA4434 as the best candidates. Furthermore, the best candidates prioritized were shown to strongly interact with the same residues that interacted with hTS substrate and cofactor. |
---|---|
MeSH term(s) | Humans ; Thymidylate Synthase/chemistry ; Molecular Docking Simulation ; Ligands ; Protein Binding |
Chemical Substances | Thymidylate Synthase (EC 2.1.1.45) ; Ligands |
Language | English |
Publishing date | 2023-08-09 |
Publishing country | United States |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 1396450-1 |
ISSN | 1873-4243 ; 1093-3263 |
ISSN (online) | 1873-4243 |
ISSN | 1093-3263 |
DOI | 10.1016/j.jmgm.2023.108568 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
Zs.A 3491: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.