Modeling of the chiroptical response of chiral amino acids in solution using explicit solvation and molecular dynamics

Molecular dynamics (MD) simulations and TDDFT linear response computations were employed to model the molar rotations of the zwitterionic forms of glycine, alanine, proline, and phenylalanine in aqueous solution. The MD simulations inherently take into account averaging the chiroptical response of different amino acid conformers and also allow the effects from vibrational distortions and explicit solvent perturbations on the optical rotation to be modeled. The results show that the chiroptical response correlates strongly to the conformations of these molecules relative to their carboxylate functional groups. Additionally, the molar rotation of phenylalanine shows a correspondence to the molecule's internal rotation about its phenyl group. These findings may be rationalized with established and revised "sector rules" for optical activity.