Site dependence of the binding energy of water to indole: Microscopic approach to the side chain hydration of tryptophan

A microscopic approach to the in vacuo energetics of the binding of a water molecule to the side chain of tryptophan, modeled by an indole molecule, i s presented. Two binding sites have been studied, the most bound one, which corresponds to the conventional NH-OH2 hydrogen bond and a slightly less b ound, so-called pi-type hydrogen bond in which the hydrogen atoms interact with the pi aromatic ring of indole. The structure of these two complexatio n sites as well as the potential energy surface has been obtained by a semi empirical model coupled with efficient procedures for the exploration of th e surface. The H-bonded complex was observed in the supersonic expansion, a nd its binding energy (4.84 +/- 0.23 kcal/mol) was measured using a laser t wo-color photofragmentation technique. The nonstandard H-bonded complex, no t observed with indole, was observed with 1-methylindole, a substituted ind ole, in which the formation of the conventional bond is hindered. Its bindi ng energy, measured with a similar accuracy (4.10 +/- 0.14 kcal/mol), can b e used as a fair estimate of the binding energy of the pi-type complex of i ndole-water, as suggested by our calculations. The small difference in the binding energy between the two gas-phase complexes suggests that, although being traditionally considered as a highly hydrophobic residue, the side ch ain of tryptophan is not only able to established a H-bond with a proton ac ceptor bur also can exhibit significant nonstandard interactions with an aq ueous environment.