Does Thermal Breathing Affect Collision Cross Sections of Gas-Phase Peptide Ions? An Ab Initio Molecular Dynamics Study

Abstract

Ab initio molecular dynamics (AIMD) with density functional theory (DFT) was applied to explore conformational motions and collision cross sections (Ω) of folded (2) and extended (7) conformers of doubly charged peptide ions, (Ala–Ala–Leu–Arg + 2H)2+, in the gas phase at 300 and 473 K. The experimental Ω of (Ala–Ala–Leu–Arg +2H)2+ was measured as 149 ± 1.2 Å2 at 298 K. Thermally distributed mean values of Ω for 2 and 7 at 300 and 473 K were only 0.8–1.1% larger than for the equilibrium 0 K structures. Long (>10 ps) trajectory calculations indicated entropy-driven conformational change of 2 to 7 that occurred at random within a ~ 4 ps time window. The experimental Ω was found to fit the calculated population averaged values for 2 and 7, indicating a rapid conformer interconversion. Overall, thermal breathing had only a minor effect on the peptide ion collision cross sections.

Ion Mobility-Mass Spectrometry of Iodine Pentoxide–Iodic Acid Hybrid Cluster Anions in Dry and Humidified Atmospheres

“…Calculation results are shown for multiple potential cluster ion structures. Consistent with prior studies on the influence of cluster structure on the CCS,38 differences in the predicted CCSs for different structures are significantly smaller than the influence of scattering model. Results show clearly that DHSS model predictions are in good agreement with measurements.…”

Replacing H+by Na+or K+in phosphopeptide anions and cations prevents electron capture dissociation

“…The wider reach of K16 compared to that of the N terminus is consistent with its long and flexible sidechain, although it is unlikely that a single peptide ion structure can account for the observed fragmentation pattern as the simultaneous binding of nine residues to K16 is geometrically infeasible. Instead, the niECD data indicate multiple phosphopeptide ion structures that could either be separated by high barriers 61 – 65 or rapidly interconvert at room temperature 66 depending on the stability of each structure and thus the strength and number of intermolecular hydrogen bond and salt bridge interactions. 44 , 45 , 67 , 68 However, the lack of c , z ˙ or c ˙, z fragments from cleavage at sites 4–6 suggests that the (M – 2H) 2– zwitterion structures are similar in that the protonated N terminus interacts only with the first three residues, and protonated K16 interacts only with residues 7–15, thereby forming two clusters of salt bridge and ionic hydrogen bond networks around the positively charged sites ( Scheme 2 ) that are separated by at least residues 4–6.…”

A parallelized molecular collision cross section package with optimized accuracy and efficiency

“…Our methodology is supported by numerous studies who approximate molecular motions through targeted molecular dynamics or PES searches, where inclusion of populationaveraged (i.e., Boltzmann-weighted) CCSs results in improved matches with experiment. 12,21,69,70 While no method is free of systematic bias, the compounds present in the calibration and validation set were carefully selected to exhibit a diverse set of functional groups that encompass the molecular space defined by the MMFF94 forcefield. The derivation of vdW parameters relied on rigorous structural modelling of compounds and can be regarded as a comprehensive exploration of the vdW potential surface.…”