Here is a review about native mass spectrometry and H-D exchange methods.

Article Mass spectrometric analysis of protein–ligand interactions

Like everything (including Schrodinger's cat) the answer depends! MS is like taking a hammer to a molecule. You are fragmenting it and putting a charge on that fragment. Somewhere in that 'soup' is a fragment of unbound protein and protein bound to that ligand.

In many cases the scientist uses CID (collision induced daughters) to detect and quantify these fragments.

Hi,

As per my experience of Mass Spectrometry, it might not be only suitable technique for your study. If your ligand is same all the time then you will surely get same peaks in all runs. Moreover, change in receptor molecule might give you additional peaks. I will suggest you to use UV-Vis spectrophotometry prior to MS. If you find significant differences in peaks in UV-Vis, then they should be differentiated using MS. Remember that MS works on fragmentation pattern using different fragmenting techniques. It doesn't matter what you inject, since the instrument will break all molecules into lowest possible fragments.

Hello Ade,

several Electrospray based methods have been described to do native MS since seminal work of Ganem, Li and Henion from 1991, linked below.

Article Detection Of Noncovalent Receptor Ligand Complexes By Mass-S...

So, yes, it is possible to achieve mild ionization to avoid fragmentation and study non-covalent molecular associations by MS. Have a look to these other more recent works:

Article Detection of a receptor‐ligand non‐covalent complex using a ...

Article Selective Detection of Specific Protein-Ligand Complexes by ...

In the other hand, fragmentation will be necessary to get information about ligand binding sites, in top-down proteomics approach. Dissociation methods, such as Electron-Capture Dissociation (ECD), have been used to do that. Have a look to the following article:

Article Top-down ESI-ECD-FT-ICR mass spectrometry localizes noncoval...

Another good review in this issue is:

Article Current Limitations in Native Mass Spectrometry Based Struct...

Hope it helps.

The interactions of small molecules with proteins (protein–ligand interactions) mediate various biological phenomena including signal transduction and protein transcription and translation. Synthetic compounds such as drugs can also bind to target proteins, leading to the inhibition of protein–ligand interactions. These interactions typically accompany association–dissociation equilibrium according to the free energy difference between free and bound states; therefore, the quantitative biophysical analysis of the interactions, which uncovers the stoichiometry and dissociation constant, is important for understanding biological reactions as well as for rational drug development. Mass spectrometry (MS) has been used to determine the precise molecular masses of molecules. Recent advancements in MS enable us to determine the molecular masses of protein–ligand complexes without disrupting the non-covalent interactions through the gentle desolvation of the complexes by increasing the vacuum pressure of a chamber in a mass spectrometer. This method is called MS under non-denaturing conditions or native MS and allows the unambiguous determination of protein–ligand interactions. Under a few assumptions, MS has also been applied to determine the dissociation constants for protein–ligand interactions. The structural information of a protein–ligand interaction, such as the location of the interaction and conformational change in a protein, can also be analyzed using hydrogen/deuterium exchange MS. In this paper, we briefly describe the history, principle, and recent applications of MS for the study of protein–ligand interactions.

Entedhar Sarha : Please stop plagiarizing other people's published work and presenting it as your own on this and other websites.