Bifunctional probes can be used to react specifically with certain amino acid side chain groups that are positioned in proximity to each other and within a distance defined by the length of the employed probe. Reaction of the cross linking reagent with each side chain links the amino acids together chemically providing a snap shot of the conformation of the protein. Using bottom up proteomics approaches, the cross linked peptides can be detected and charaterised providing a distance constraint between the two parts of the molecule which could potetially be far apart in the primary sequence. Cross linking is complementary to other structural approaches such as NMR and X-ray crystallography. It is particulalry useful when sample amounts are limited or the system in question is intransigent to analyses by other techniques.