STRUCTURAL STUDIES OF VIRUSES BY LASER RAMAN-SPECTROSCOPY .36. CYSTEINE CONFORMATION AND SULFHYDRYL INTERACTIONS IN PROTEINS AND VIRUSES .2. NORMAL COORDINATE ANALYSIS OF THE CYSTEINE SIDE-CHAIN IN MODEL COMPOUNDS

We report vibrational normal mode analyses of cysteine and several model mercaptans containing the -CHRCH2SH group (R = H or CH3). The results provide a basis for assigning observed Raman frequencies to specific conformers of the cysteinyl C(alpha)-C(beta)-S-H side chain and for assessing SH hydrogen bonding with appropriate donor and acceptor groups. Vibrational spectra and normal coordinate analyses of L-cysteine, 1-propanethiol (1PT), 1-propanedeuteriothiol (1PT-d1), and 2-methyl-1-propanethiol 2M1PT) and corresponding experimental data on 2-methyl-2-propanethiol derivatives (2M2PT and 2M2PT-d1) indicate that conformation-sensitive modes occur in both the C-S stretching (600 < sigma(CS) < 800 cm-1) and the S-H stretching (2500 < sigma(SH) < 2650 cm-1) regions of the Raman spectrum. Using a generalized valence force field, we have correlated the side-chain torsion angle (X1) of the C(alpha)-C(beta) bond with sigma(SH), and the torsion angle (X2) of the C(beta)-S bond with both sigma(CS) and sigma(SH). The principal conclusions from the present study are as follows: (i) The force field obtained from 1PT is satisfactorily transferable to 2M1PT and L-cysteine and reproduces the observed trends for sigma(SH) and sigma(CS) of these molecules. (ii) acs can be shifted substantially (up to 50 cm-1) by changes in X1, but is less sensitive (< 10 cm-1) to changes in X2. (iii) sigma(SH) is perturbed sufficiently by changes in X2 to account for previously reported frequency differences in Raman SH bands of cysteinyl gauche rotamers.1 Correlations are proposed for the dependence of both sigma(CS) and sigma(SH) upon conformation of the C(alpha)-C(beta)-S-H network. These correlations are expected to be useful for determining cysteine side-chain environments in proteins and their assemblies, including virions and viral precursors.