PXD026297-1

PXD026297 is an original dataset announced via ProteomeXchange.

Title	Assessing target engagment using proteome-wide solvent shift assays
Description	Recent 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.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_04:19:32.820.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jonathan Van Vranken
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-26 23:39:56	ID requested
⏵ 1	2022-02-17 04:19:33	announced

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]

submitter keyword: target enagagement

Steven Gygi
contact affiliation	Department of Cell Biology, Harvard Medical School
contact email	steven_gygi@hms.harvard.edu
lab head
Jonathan Van Vranken
contact affiliation	Harvard Medical School
contact email	van@hms.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026297
     1. Label: PRIDE project
     2. Name: Assessing target engagment using proteome-wide solvent shift assays