DFT conformational study of cysteine in gas phase and aqueous solution

Abstract Different conformers of cysteine in gas phase are investigated at the DFT B3LYP/6-31G ∗ and B3LYP/6-311++G ∗∗ levels. The effect of the solvent is simulated by using the Onsager and polarizable continuum (PCM) models within the self-consistent reaction field method (SCRF) at the B3LYP/6-31G ∗ level. Specifically, five neutral forms, two anions and one zwitterion were analysed. Both, in gas phase and solution the most stable normal form has the carboxyl group directed toward the amino group. In accord with the experiment, the PCM model predicts that the most stable structure in solution is a zwitterion, a species that does not exist or has a very small stability in gas phase. A major stabilization in solution is also predicted for the zwitterionic form of anionic cysteine. Thus the PCM model renders correct stability order of the different conformers in solution, while the Onsager model does not, which is due to the underestimation of the electrostatic contributions to the solute–solvent interaction for the zwitterions.