Can Mass Spectrometry Reveal the 3D Structure of Proteins?

Mass spectrometry is a technique that obtains structural information of compounds by determining the ratio of molecular ion mass to quantity. In theory, this method should be sensitive only to the mass and charge of the substance, not the shape and structure of the substance. So why do we discuss mass spectrometry with the three-dimensional structure of proteins? The reason is that mass spectrometry of proteins is not a simple task of obtaining a mass value, but it requires a series of ion fragment patterns to infer the sequence and structure of the protein.

 

Complexity of Protein Mass Spectrometry

Proteins are large biological molecules made up of a series of amino acids linked in a specific order, and their three-dimensional structure depends on the order and interactions of the amino acids. Currently, although mass spectrometry can accurately measure the mass of amino acids and even infer the sequence of the amino acid chain, it is difficult to directly observe the three-dimensional structure of proteins. Because, in the mass spectrometry experiment, proteins generally need to be ionized and fly in high vacuum, which leads to serious distortion of the three-dimensional structure of proteins.

 

Limitations and Possibilities of Mass Spectrometry

In summary, although mass spectrometry can provide us with the information of protein sequence, it can't directly reflect its unique three-dimensional structure, which is a limitation of mass spectrometry in protein detection. However, this does not mean that mass spectrometry has no potential in revealing the three-dimensional structure of proteins. Native mass spectrometry is a detection method that protects the original structure of proteins. Although it can't directly analyze the specific three-dimensional shape of proteins at present, it can infer the assembly form and steady state of proteins by measuring the mass of proteins.

 

Of course, the path of scientific development is always full of surprises and challenges. With the development of science and technology and the deepening understanding of mass spectrometry by researchers, we believe that one day we will be able to reveal the three-dimensional structure of proteins more intuitively through mass spectrometry. This will provide a more accurate basis for disease diagnosis and drug design.