The structure of the gas-phase tyrosine-glycine dipeptide

The structural preferences of the neutral dipeptide Tyr-Gly have been investigated using a hierarchical selection scheme. This scheme consists of a hierarchy of increasingly more accurate electronic structure methods (single-point HF/3-21G* energy calculation, HF/3-21G* geometry optimization, B3LYP/6-31+G* geometry optimization, MP2/6-31+G* single-point energy calculation, and MP2/6-31+G* geometry optimization). The conformers are sorted according to their single-point or optimized energy, and only the most stable conformers according to one level are taken through to the next level of calculation. The defining structural characteristics in the 20 most stable Tyr-Gly conformers are the presence or absence of a folded arrangement of the peptide backbone ('book') and an OH (.) (.) (.) O hydrogen bond between the C-terminal hydroxyl group and the carbonyl oxygen of tyrosine ('OHO'). The most stable conformer is of the book/OHO type. MP2 geometry optimization significantly alters the structure of the book-type conformers, increasing their degree of foldedness. Thus, care has to be taken when applying standard density functionals like B3LYP in structural studies of peptides with aromatic side chains.