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I'm familiar with various ways to probe for specific proteins in a given sample(antibody/antigen, aptamers, etc). But these techniques seem to require an understanding of what protein you're looking to probe.

Is there a way to probe for unknown proteins? Some sort of molecule that enables proteins to bind, and through many interrogation reactions would allow us to know what that protein is?

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If you have no idea: Proteomics using Mass spectrometry

Mass spectrometry is a powerful method that (in theory) identifies every proteins in a given solution. However, I don‘t know how robust this method is in terms of sensitivity in the presence of large background signals. Usually, people pre-process the sample, e.g. they separate the raw protein extract in a 2D PAGE (polyacrylamid gel electrophoresis), separating the proteins by size and isoelectric point in a gel. Then they cut the gel into pieces, extract specific proteins and then identify protein fractions using mass spectrometry.

Advanced mass spectrometry methods seem to be able to identify proteomes from imaged tissue samples Ryan et al. 2019

A pulldown assay is also powerful method to pre-isolate unknown components of a protein complex. But for that you need one component or an antibody that binds to a component of the protein complex.

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