Assessing the role of tryptophan residues in the binding site

Instead of looking at the interfacial area as a measure of the extent of a protein-protein recognition site, a new procedure has been developed to ide ntify the importance of a specific residue, namely tryptophan, in the bindi ng process. Trp residues which contribute more towards the free energy of b inding have their accessible surface area reduced, on complex formation, fo r both the main-chain and side-chain atoms, whereas for the less important residues the reduction is restricted only to the aromatic ring of the side chain. The two categories of residues are also distinguished by the presenc e or absence of hydrogen bonds involving the Trp residue in the complex. A comparison of the observed change in the accessible surface area with the v alue calculated using an analytical expression provides another way of char acterizing the Trp residues critical for binding and this has been used to identify such residues involved in binding non-proteinaceous molecules in p rotein structures.