Computational discovery of BRD4 inhibitors for neuroblastoma therapy using pharmacophore screening and molecular simulations
Iqra Ali, Mervt Almostafa, Faheem Abbas, Nancy S. Younis, Azmat Ali Khan, Galal Yahya
TL;DR
This paper uses computational methods to discover new BRD4 inhibitors that could be effective in treating neuroblastoma.
Contribution
The study introduces a novel integrated pharmacoinformatic strategy combining pharmacophore screening and molecular simulations to identify BRD4 inhibitors.
Findings
Pharmacophore screening identified 1089 hits, with top ten compounds showing strong binding affinities to BRD4.
MD simulations confirmed the stability of the top two compounds, suggesting their potential as lead compounds for neuroblastoma therapy.
Abstract
BRD4 (“Bromodomain-containing protein 4”), a recognized gene regulator, is an attractive target for therapeutic development, particularly for the management of neuroblastoma. An integrated pharmacoinformatic strategy for the development of new BRD4 inhibitors is examined in this research. Pharmacophores were used to digitally screen five databases, and the current study aims to determine the best binding modes by docking the screened hits to the BRD4 active site. Using the BRD4 protein co-crystal ligand (73B) (PDB ID: 4BJX) as a template, pharmacophore hypotheses were produced. Five databases were subjected to a pharmacophore-based virtual screening process, and 1089 hits that satisfied the screening requirements were selected for docking against the BRD4 receptor by using the SP module of the Glide tool. The top ten docked compounds with the highest binding affinities, ranging from −…
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Taxonomy
TopicsProtein Degradation and Inhibitors · Multiple Myeloma Research and Treatments · Ubiquitin and proteasome pathways