First-principles computation of electronic circular dichroism spectra of solvated molecules using RISM-SCF-cSED.

Area of Science:

• Computational Chemistry
• Spectroscopy
• Biomolecular Modeling

Background:

• Accurate prediction of electronic circular dichroism (ECD) spectra is crucial for characterizing chiral molecules.
• Existing computational methods often struggle to quantitatively reproduce experimental ECD spectra, especially for molecules in solution.

Purpose of the Study:

• To develop and validate a practical first-principles computational protocol for calculating ECD spectra of chiral molecules in aqueous solution.
• To establish a computationally efficient platform for predicting ECD spectra of solvated molecules.

Main Methods:

• Combining time-dependent density functional theory (TDDFT) with the reference interaction site model self-consistent field with constrained spatial electron density (RISM-SCF-cSED).
• Utilizing molecular dynamics-based conformational sampling when necessary.
• Demonstrating the protocol on D-lactic acid and the alanine tetramer (Ac-Ala4-NMe).

Main Results:

• The RISM-SCF-cSED/TDDFT protocol accurately reproduced the ECD spectrum of D-lactic acid.
• Quantitative reproduction of the ECD spectrum for the α-helical state of Ac-Ala4-NMe was achieved by incorporating explicit solute water hydrogen-bonding structure.
• The method proved effective for both small chiral molecules and solvated biomolecules.

Conclusions:

• The developed RISM-SCF-cSED/TDDFT combined approach provides a general and computationally efficient platform for predicting ECD spectra of solvated molecules.
• This protocol enables accurate characterization of chiral molecules in aqueous environments.
• The study highlights the importance of explicit solvent modeling for quantitative spectral predictions.