# Fully Atomistic Modeling in Computational Spectroscopy: Tryptophan in Aqueous Solution as a Test Case

## TL;DR

This paper introduces a detailed computational method to simulate various spectroscopic properties of tryptophan in water, showing good agreement with experimental results.

## Contribution

A novel multiscale computational protocol combining DFT and polarizable embedding models for accurate spectroscopic simulations.

## Key findings

- The protocol successfully reproduces UV–vis and ECD spectra of tryptophan in aqueous solution.
- Computed NMR chemical shifts and vibrational spectra align well with experimental data.
- Accurate solvent treatment is crucial for chiroptical and magnetic properties.

## Abstract

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.