A Method for the detection of the conformational state of a protein contained in a complex mixture of further proteins and/or other biomolecules, is proposed as well as assays for such a method. The method comprises the following steps: (1) Limited proteolysis of the complex mixture under a condition where the protein is in the conformational state to be detected leading to a first fragment sample; (2) Denaturation of the first fragment sample to a denaturated first fragment sample; (3) Complete fragmentation of the denaturated first fragment sample in a digestion step to a completely fragmented sample; and (4) Analytical analysis of the completely fragmented sample for the determination of fragments characteristic of having been the result both the limited proteolysis of step 1 as well as of the complete fragmentation in the digestion step 3. for the determination of the conformational state.