PXD071156-1

PXD071156 is an original dataset announced via ProteomeXchange.

Title	Validation of Solvent Proteome Profiling for Antimalarial Drug Target Deconvolution
Description	Malaria remains a global health threat, with rising drug resistance accelerating the urgent need for new therapeutics. Target elucidation is a critical step in antimalarial drug discovery, enabling a deeper understanding of the molecular mechanisms of action of both existing and novel compounds. This study validates solvent-induced proteome profiling (SPP) as a proteomics-based approach for identifying drug-protein interactions in Plasmodium falciparum. SPP de-tects shifts in protein stability induced by ligand binding, allowing the identification of drug target/s without the need for compound modifications. Here, we successfully generated solvent denaturation curves for the P. falciparum pro-teome, and demonstrated the utility of SPP with five antimalarial compounds: pyrimethamine, atovaquone, cipar-gamin, MMV1557817 and OSM-S-106. In addition to measuring each compound’s impact across the full denatura-tion curve, investigating protein levels at individual solvent percentages preserved specific stability changes that would otherwise be masked in pooled analyses performed by integral SPP. This strategy was critical for the identifi-cation of the cipargamin target, non-SERCA-type Ca2+-transporting P-ATPase (PfATP4). Notably, we propose live-cell treatment SPP as a novel approach, demonstrating its ability to identify the validated target of pyrimethamine, bifunctional dihydrofolate reductase-thymidylate synthase (PfDHFR), with high specificity. We also introduced the novel one-pot mixed-drug SPP, which enables the evaluation of multiple drugs within a single lysate and experi-mental setup. This alternative method simplifies the experimental workflow and includes positive controls to affirm the performance of the experiment. Overall, this study demonstrates that SPP can be successfully applied in both ly-sate and live-cell treatment conditions to elucidate drug targets in P. falciparum, as well as providing additional in-formation regarding the mechanisms of drug action, offering insights for the optimisation of existing antimalarials and the development of novel therapies.
HostingRepository	PRIDE
AnnounceDate	2025-11-26
AnnouncementXML	Submission_2025-11-26_00:56:31.868.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yijia Ji
SpeciesList	scientific name: Plasmodium falciparum (isolate 3D7); NCBI TaxID: NEWT:36329;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-24 17:49:17	ID requested
⏵ 1	2025-11-26 00:56:32	announced

10.1016/J.IJPDDR.2025.100626;

submitter keyword: Malaria

Plasmodium falciparum

Solvent-induced Proteome Profiling (SPP)

Drug Target Deconvolution

Orbitrap Astral MS

Antimalarial Compounds

Darren J Creek
contact affiliation	Drug Delivery, Disposition and Dynamics; Monash Institute of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University (Parkville campus)
contact email	darren.creek@monash.edu
lab head
Yijia Ji
contact affiliation	Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences
contact email	jessica.ji1@monash.edu
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/2025/11/PXD071156

PRIDE project URI

• PRIDE
  1. PXD071156
     1. Label: PRIDE project
     2. Name: Validation of Solvent Proteome Profiling for Antimalarial Drug Target Deconvolution