PXD041587-1

PXD041587 is an original dataset announced via ProteomeXchange.

Title	Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells
Description	Chemical modulation of protein function enables a mechanistic understanding of biological circuits and represents the foundation of most medicines. However, despite major efforts over decades of research, around 80% of the human proteome still lack functional ligands. Chemical proteomics allowed the advancement of fragment-based ligand discovery (FBLD) towards cellular systems and emerged as a promising strategy to detect reversible fragment-protein interactions that can be furnished into bioactive chemical probes. Limitations in scale and throughput have, however, stymied the interpretation of the resulting ligandability maps, thus complicating the identification of specific and actionable fragment-protein interactions. Here, we report reversible, global ligandability maps for 435 structurally different fragments, collectively representing 6739 discrete interactions. We benchmark the dataset by showing that identified fragments can be advanced to active chemical probes. Integrating multi-layered ligandability portraits with artificial intelligence (AI) and machine learning (ML) enabled quantitative and qualitative predictions of fragment interactomes via chemically interpretable models. The resulting, interactive catalogue of fragment-protein interactions and predictive models is expected to expedite ligand discovery efforts in a community-wide fashion and should facilitate the pursuit of hitherto undrugged target proteins.
HostingRepository	PRIDE
AnnounceDate	2024-05-07
AnnouncementXML	Submission_2024-05-07_09:36:56.875.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD041587
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Nara Marella
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; L-methionine removal; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-17 13:30:44	ID requested
⏵ 1	2024-05-07 09:36:57	announced

10.6019/PXD041587;

Offensperger F, Tin G, Duran-Frigola M, Hahn E, Dobner S, Ende CWA, Strohbach JW, Rukavina A, Brennsteiner V, Ogilvie K, Marella N, Kladnik K, Ciuffa R, Majmudar JD, Field SD, Bensimon A, Ferrari L, Ferrada E, Ng A, Zhang Z, Degliesposti G, Boeszoermenyi A, Martens S, Stanton R, M, ü, ller AC, Hannich JT, Hepworth D, Superti-Furga G, Kubicek S, Schenone M, Winter GE, Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science, 384(6694):eadk5864(2024) [pubmed]

10.1126/science.adk5864;

submitter keyword: machine learning, bioactive, drug, Screening, chemical probe, fragment-protein interaction, FBLD, AI,Chemical Proteomics, Ligandability

Georg Winter
contact affiliation	Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM)
contact email	GWinter@cemm.oeaw.ac.at
lab head
Nara Marella
contact affiliation	CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
contact email	nara.marella@outlook.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/05/PXD041587

PRIDE project URI

• PRIDE
  1. PXD041587
     1. Label: PRIDE project
     2. Name: Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells