I would like to know if there is an assay which could allow us to analyse a protein before it has assumed its 3D functional form. While studying structural biology, I only came to know the forces that stabilize the structure, but not the gap between the original random coil and the protein in its native form.
Theoretically by molecular modeling -- see the works by Harold Scheraga: https://www.ncbi.nlm.nih.gov/pubmed/?term=Harold+Scheraga%5BAuthor%5D
Note: An unfolded protein is not a random coil.
Fitzkee & Rose (2004) PNAS 101:12497-12502; emphasis mine:
denatured proteins are biased toward specific conformations, in ... conflict with the random-coil model
This is difficult. You need to use stopped flow methods(CD, fluorescence, NMR) or single molecule methods. What exactly do you want to know about the protein? I mean, it would be hard to get the complete accurate 3d structure, as you can't crystallize an intermediate. Apart from that, if you have an accurate folding simulation for that protein, you can of course see what the common intermediates are. I am sure that if you have the Rosetta protein folding algorithms, you know the final structure, you can calculate likely intermediates with some accuracy. Then you may be able to use stopped flow methods to try to refuse those findings. If that fails, you may be able to make a convincing case that you found those intermediates.
Some of the information contained in this post requires additional references. Please edit to add citations to reliable sources that support the assertions made here. Unsourced material may be disputed or deleted.