Computational Modeling of the Nitrile Stretching Vibration of 5-Cyanoindole in Water.

The bandwidth of the nitrile (C≡N) stretching vibration of 5-cyanotryptophan shows a significant broadening upon hydration. Thus, it has been proposed to be a useful infrared probe of the local hydration environment of proteins. However, the molecular mechanism underlying this hydration-induced spectral broadening is not known, making interpretation of the experimental results difficult. Herein, we investigate how interactions of water with various sites of 5-cyanoindole, the sidechain of 5-cyanotryptophan, affect its C≡N stretching vibration via a combined electronic structure/molecular dynamics approach. It is found that, besides those interactions with the nitrile group, interactions of water with the indole ring also play a significant role in mediating the C≡N stretching frequency. Thus, this study provides a molecular basis for understanding how hydration affects the C≡N stretching band of 5-cyanotryptophan. In addition, an empirical model, which includes interactions of water with both the nitrile and indole groups, is developed for predicting the C≡N stretching vibrational band via molecular dynamics simulations.