9IFW

FSP1 (tetrapod ancestor) bound to FAD and NAD+ and compound 4

This is a non-PDB format compatible entry.

Summary for 9IFW

• Entry DOI: 10.2210/pdb9ifw/pdb
• Descriptor: FSP1 (Tetrapod ancestor), FLAVIN-ADENINE DINUCLEOTIDE, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (10 entities in total)
• Functional Keywords: flavin, nad, coenzyme q, ferroptosis, myristoylation, inhibitor discovery, oxidoreductase
• Biological source: Mammalia
• Total number of polymer chains: 2
• Total formula weight: 83873.54

Authors

Cecchini, D.,Mattevi, A. (deposition date: 2025-02-18, release date: 2026-03-04, Last modification date: 2026-09-16)

Primary citation

Cecchini, D.,Nigam, A.,Tang, M.,Reis, J.,Koop, M.,Gottinger, A.,Nicoll, C.R.,Wang, Y.,Jayaraj, A.,Cinaroglu, S.S.,Torner, R.,Malets, Y.,Gehev, M.,Padmanabha Das, K.M.,Churion, K.,Kim, J.,Thomas, N.,Li, Y.,Seo, H.S.,Dhe-Paganon, S.,Secker, C.,Haddadnia, M.,Hasson, A.,Li, M.,Kumar, A.,Levin-Konigsberg, R.,Choi, E.B.,Shapiro, G.I.,Cox 3rd, H.,Sebastian, L.,Braithwaite, C.,Bashyal, P.,Radchenko, D.S.,Kumar, A.,Yang, L.,Aquilanti, P.Y.,Gabb, H.,Alhossary, A.,O'Neill, E.,Wagner, G.,Aspuru-Guzik, A.,Moroz, Y.S.,Kalodimos, C.G.,Fackeldey, K.,Schuetz, J.D.,Mattevi, A.,Arthanari, H.,Gorgulla, C.
AI-enhanced adaptive virtual screening of large libraries for ligand discovery.
Nat.Biotechnol., 2026

PubMed Abstract: Ultralarge virtual screenings (ULVSs) evaluate billions of molecules for drug discovery but face cost, flexibility and scalability limits. We introduce AdaptiveFlow, an open-source platform that makes ULVSs more accessible, scalable and efficient and supports artificial intelligence (AI) and machine learning (ML) method development. AdaptiveFlow provides a screening-ready version of the Enamine REAL Space, to our knowledge the largest library of ready-to-dock, drug-like molecules, comprising 69 billion compounds, also available in SELFIES format. An 18-dimensional grid of molecular properties prioritizes promising chemical subspaces, with optional active learning, reducing computational costs by orders of magnitude. AdaptiveFlow integrates >1,500 docking protocols, including GPU-accelerated and ML-based methods, and achieves near-linear scaling on up to 5.6 million CPUs in the Amazon Web Services cloud. We identified nanomolar inhibitors of two disease-relevant targets, ferroptosis suppressor protein 1 (FSP1) and poly(ADP-ribose) polymerase 1. Co-crystal structures provided mechanistic insights into FSP1 inhibition. AdaptiveFlow enables drug discovery at unprecedented scale and supports the development of AI-driven methods.

PubMed: 42680826
DOI: 10.1038/s41587-026-03217-x

Experimental method

X-RAY DIFFRACTION (1.74 Å)