Fully atomistic modeling in computational spectroscopy: tryptophan in aqueous solution as a test case

We present a multiscale computational protocol for the simulation of a wide range of spectroscopic properties─electronic, magnetic, and vibrational─of zwitterionic l-tryptophan in aqueous solution. The approach combines density functional theory (DFT) for the solute with polarizable embedding models (QM/FQ and QM/FQFμ) for the solvent, and incorporates extensive conformational sampling via classical molecular dynamics. The protocol successfully reproduces UV-vis and ECD spectra, including the characteristic S0 → S1 transition and chiroptical features, and captures the negative optical rotation at the sodium D-line with good agreement to experiment. NMR chemical shifts and spin-spin couplings are also computed, and a hybrid QM/FDE/FQFμ scheme is employed to improve the description of solvent-sensitive nuclei. Vibrational spectra (IR, Raman, and ROA) are calculated and analyzed, with all models yielding results consistent with experimental data where available. The comparison between QM/FQ and QM/FQFμ highlights the importance of accurate solvent treatment, especially for chiroptical and magnetic properties.