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PXD026297 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAssessing target engagment using proteome-wide solvent shift assays
DescriptionRecent advances in mass spectrometry (MS) have enabled quantitative proteomics to become a powerful tool in the field of drug discovery, especially when applied toward proteome-wide target engagement studies. Similar to temperature gradients, increasing concentrations of organic solvents stimulate unfolding and precipitation of the cellular proteome. This property can be influenced by physical association with ligands and other molecules, making individual proteins more or less susceptible to solvent-induced denaturation. Herein, we report the development of proteome-wide solvent shift assays by combining the principles of solvent-induced precipitation (Zhang et al., 2020) with modern quantitative proteomics. Using this approach, we developed solvent proteome profiling (SPP), which is capable of establishing target engagement through analysis of SPP denaturation curves. We readily identified the specific targets of compounds with known mechanisms of action. As a further efficiency boost, we applied the concept of area-under-the-curve analysis to develop solvent proteome integral solubility alteration (solvent-PISA) and demonstrate that this approach can serve as a reliable surrogate for SPP. We propose that by combining SPP with alternative methods, like thermal proteome profiling, it will be possible to increase the absolute number of high-quality melting curves that are attainable by either approach individually thereby increasing the fraction of the proteome that can be screened for evidence of ligand binding.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJonathan Van Vranken
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-05-26 23:39:56ID requested
12022-02-17 04:19:33announced
Publication List
Van Vranken JG, Li J, Mitchell DC, Navarrete-Perea J, Gygi SP, Assessing target engagement using proteome-wide solvent shift assays. Elife, 10():(2021) [pubmed]
Keyword List
submitter keyword: target enagagement
Contact List
Steven Gygi
contact affiliationDepartment of Cell Biology, Harvard Medical School
contact emailsteven_gygi@hms.harvard.edu
lab head
Jonathan Van Vranken
contact affiliationHarvard Medical School
contact emailvan@hms.harvard.edu
dataset submitter
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Dataset FTP location
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