Method and tools for the determination of conformations and conformational changes of proteins and of derivatives thereof

A method for detection of a conformational state of at least one protein, said at least one protein being contained in a complex mixture of further proteins and/or other biomolecules, wherein said at least one protein in said complex mixture has been subjected to a condition inducing a structural change in said at least one protein, comprising, if needed after at least one of an extraction and/or lysis step, the following sequence of steps:

• 1. limited proteolysis of the complex mixture under a condition in which the at least one protein is in the original conformational state to be detected leading to a first fragment sample;
• directly followed by
• 2. removal of large peptides and proteins or other biomolecules from said first fragment sample to form an enriched fragment sample;
• 3. analytical analysis of the enriched fragment sample for the determination of fragments characteristic of having been the result of the limited proteolysis of step 1. as well as remaining after the removal step 2. for the determination of the conformational state of said at least one protein.