Vibrational optical activity of cysteine in aqueous solution: a comparison of theoretical and experimental spectra

Raman, Raman optical activity (ROA), infrared (IR), and vibrational circular dichroism (VCD) spectra of cysteine in aqueous solution have been measured and calculated by means of density functional theory. The influence of aqueous environment on the spectra of cysteine has been simulated by means of implicit (polarizable continuum model) and explicit (molecular dynamics, solute-solvent clusters) methods. The results indicate that, while PCM reproduces some of the features of the spectra, the best description is rendered by the microsolvation model (solute-solvent clusters). The shape of the bands is in some cases more correctly reproduced by MD, but their intensities and positions are not, since these simulations are hampered by the standard force field being parametrized for conformations of peptides rather than isolated amino acids. The calculated ROA spectra have been used to extract conformational ratios from the experimental spectra, and again, the best results (as verified by simulations of other spectra) have been obtained when using the microsolvation model. This procedure renders three zwitterion conformers dominating the spectra of hydrated cysteine, of conformational ratios of 35, 33, and 24%, respectively.