ON THE INFLUENCE OF SECONDARY STRUCTURE ON THE ALPHA-C-H BOND-DISSOCIATION ENERGY OF PROLINE RESIDUES IN PROTEINS - A THEORETICAL-STUDY

Ab initio computations (B3LYP/6-31G(D), coupled with isodesmic reactio ns) were used to predict C-alpha-H bond dissociation energies (BDEs) f or proline as a residue in a model peptide, intended to mimic the envi ronment in proteins. The environment was further constrained to mimic common proline positions in beta turns of different types. The BDEs we re found to be very dependent on the structural constraints imposed by the beta turn type, implying different structure-mediated susceptibil ities to free radical damage to proline residues. Unnatural repair of proline (inversion of chirality) was found to be thermodynamically unf avourable. The predicted BDEs for the proline C-alpha-H bond, in ki mo l(-1), to an estimated accuracy of +/-10 kJ mol(-1) are as follows: fu lly optimized trans rotamer, 368.6; fully optimized cis rotamer, 357.7 ; beta turn type I, 380.7; beta turn type II, 397.8; beta rum type II: 385.4; beta turn type VIa, 374.0; beta turn type VIb, 355.0.