MD + QM Correlations with Tryptophan Fluorescence Spectral Shifts and Lifetimes

Principles behind quenching of tryptophan (Trp) fluorescence are updated and extended in light of recent 100-ns and 1-μs molecular dynamics (MD) trajectories augmented with quantum mechanical (QM) calculations that consider electrostatic contributions to wavelength shifts and quenching. Four studies are summarized, including (1) new insight into the single exponential decay of NATA, (2) a study revealing how unsuspected rotamer transitions affect quenching of Trp when used as a probe of protein folding, (3) advances in understanding the origin of nonexponential decay from 100-ns simulations on 19 Trps in 16 proteins, and (4) the correlation of wavelength with lifetime for decay-associated spectra (DAS). Each study strongly reinforces the concept that—for Trp—electron transfer-based quenching is controlled much more by environment electrostatic factors affecting the charge transfer (CT) state energy than by distance dependence of electronic coupling. In each case, water plays a large role in unexpected ways.