The low energy tautomers and conformers of the dipeptides HisGly and GlyHis and of their sodium ion complexes in the gas phase

Publisher Website
Google Scholar
Abstract
The low-lying conformers of the dipeptides HisGly and GlyHis, and of their sodium cation complexes, have been studied with a combination of Monte Carlo search with the Amber force field and local geometry optimization at the ab initio HF/6-31G(d) level, completed with MP2(full)/6-311+G(2d,2p) energetics at the HF/6-31G(d) geometries. For each dipeptide, both the Nδ–H and Nε–H tautomers of the imidazole side chain of His were considered. For each of the four isomeric dipeptides, 20–30 conformers were fully characterized at the ab initio level. All low energy structures are found to involve H-bonding at the Nδ position of imidazole, either as a N–H donor or a N acceptor, depending upon the tautomer. In three out of the four species, the most stable conformer involves a C-terminus carboxylic acid in its less favorable trans conformation, in order to maximize intramolecular H bonding. It turns out that the lowest energy tautomer of HisGly is Nε–H, while that of GlyHis is Nδ–H. This result argues in favor of the diversity of His tautomeric states in peptides and proteins. The sodium cation complexes of both GlyHis and HisGly have been studied as well, again considering both tautomers in each case. In three out of the four species, the most stable structure involves chelation of sodium by the two carbonyl oxygens and the imidazole ring. On the contrary, the sodium complex of the Nδ–H tautomer of HisGly favors chelation to the peptidic carbonyl oxygen, the imidazole ring and the amino terminus. In the Nε–H tautomers of both peptides, the most favorable binding site of imidazole is the Nδ nitrogen, while in the Nδ–H tautomers, it is the π cloud which provides side chain interaction. As a result, both GlyHisNa+ and HisGlyNa+ favor the Nε–H tautomer of His, in contrast to what was found for the free peptides.

This publication has 38 references indexed in Scilit: