The results support that de novo design of small, site-specific protein probes for an underserved disease target is achievable using free, publicly available computational tools and minimal resources, pointing to a greater role for the public and amateur scientists to contribute to biotechnological advancement.
The convergence of docking, dynamics, and free-energy results prioritized PM2, PM3, and PM4 as promising MAP3K8 hit candidates, which require further experimental validation and lead optimization.
M. Islam, A. Iqbal, M. A. Ali et al.· Molecular diversity· 0 citations
Findings validate the diphenylpyrazine scaffold as a promising chemotype for Skp2–Cks1 inhibition and identify C3 as a strong lead for further optimization.
Emadeldin M. Kamel, A. A. Allam, H. Rudayni et al.· Journal of Computer-Aided Mo...· 0 citations
Targeting protein−protein interactions (PPIs) with shallow, extended interfaces remains challenging, as exemplified by the histone chaperone ASF1. Here, we report de novo designed d-sulfonyl-γ-AApeptide foldamers that mimic the hot-spot residues of the histone H3 C-terminal α-helix that are essential for ASF1 recogni...
Chao Hao, Xiao-Sa Wang, Kang Wang et al.· Journal of Medicinal Chemist...· 0 citations
Large-scale CRISPR base editing mutagenesis screens across 30 PI3K pathway proteins in three disease-relevant cancer cell models establish high-throughput base editing mutagenesis combined with structural analysis as a scalable strategy to delineate structure–function relationships and inform drug development.
This work presents a scalable mammalian cell-display workflow to identify AI-designed minibinders against cancer surface targets and identifies biochemical optimization beyond the binding interface as a critical requirement for translating AI-minibinders into functional applications.
B. Broske, B. McEnroe, S. C. Frechen et al.· Nature Communications· 1 citation
A crystal structure of METTL21A is solved in complex with 6m, providing structural insight into ligand recognition and supporting further structure-guided optimization and establishing a biochemically and structurally validated starting point for probing METTL21A function and a foundation for the development of cellula...
Hugo Kocek, Michal Vaško, M. Dejmek et al.· European journal of medicina...· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
