Gas-phase salt bridge interactions between glutamic acid and arginine

Abstract

The gas-phase side chain-side chain (SC-SC) interaction and possible proton transfer between glutamic acid (Glu) and arginine (Arg) residues are studied under low-temperature conditions in an overall neutral peptide. Conformation-specific IR spectra, obtained with the free electron laser FELIX, in combination with density functional theory (DFT) calculations, provide insight into the occurrence of intramolecular proton transfer and detailed information on the conformational preferences of the peptides Z-Glu-Ala n -Arg-NHMe (n = 0,1,3). Low-energy structures are obtained using molecular dynamics simulations via the simulated annealing approach, resulting in three types of SC-SC interactions, in particular two types of pair-wise interactions and one bifurcated interaction. These low-energy structures are optimized and frequency calculations are performed using the B3LYP functional, for structural analysis, and the M05-2x functional, for relative energies, employing the 6-311+G(d,p) basis set. Comparison of experimental and computed spectra suggests that only a single conformation was present for each of the three peptides.Despite the increasing spacing between the Glu and Arg residues, the peptides have several types of interactions in common, in particular specific SC-SC and dispersion interactions between the Arg side chain and the phenyl ring of the Z-cap. Comparison with previous experiments on Ac-Glu-Ala-Phe-Ala-Arg-NHMe as well as molecular dynamics simulations further suggest that the pairwise interaction observed here is indeed energetically most favorable for short peptide sequences.

Isolated Neutral Peptides

“…3.3). Vibrational couplings make the interpretation less easy, and confident assignments rely on a large spectral range (the whole amide I-III regions), especially when spectral resolution is limited, usually 1% of the IR frequency for a freeelectron source [48,54,55,66,69,79,80,82,83,95,97,105,108,131,132,136,141,142]. Difference frequency generation from table-top OPOs [52,64,90,104,120,126,127,137,139,144,145] has become a valuable alternative source to FELs, providing spectral resolutions in the cm À1 range, and solid conformational assignments have emerged from studies combining amide I/II and amide A spectral ranges (Fig.…”

“…Beyond H-bonding, IR spectroscopy is also sensitive to other interactions. A spectacular one is the formation of an intramolecular salt bridge, corresponding to an intramolecular zwitterion formation after an intramolecular proton transfer between an acidic (Glu) and a basic side chain (Arg) [105,141], revealed by the spectral carbonyl signatures.…”

A salt-bridge structure in solution revealed by 2D-IR spectroscopy

“…The method we present is also applicable for the detection of salt bridges between arginine and glutamate or aspartate in peptides and proteins. Spectral crowding due to the broadening of the amide I band in larger systems can be avoided by using isotopic labels: 15 + mode than to the low-frequency one, most likely because of their similar symmetry. Our data indicate a salt-bridge geometry in which the Gdm + and COO À moieties are coplanar.…”

“…This finding is also in agreement with experimental results in peptides in the gas phase, where planar geometries for salt bridges between Arg + and Glu À were found. 14,15 We have performed complementary ab initio calculations on the Gdm + Á Á ÁAc À dimer using Gaussian03 16 at the MP2/ 6-311+G(d) level of theory. The calculation predicts a planar geometry for the salt bridge, i.e., the three transition-dipole moments are coplanar, as shown in Fig.…”

IR Spectroscopic Techniques to Study Isolated Biomolecules

“…However, some species are difficult to bring into the gas phase without inducing fragmentation. For example, arginine-containing peptides tend to undergo substantial fragmentation [47,48]. In Fig.…”