Paper Citing NAMD - Abstract
Turecek, Frantisek; Moss, Christopher L.; Chung, Thomas W.
Correlating ETD fragment ion intensities with peptide ion conformational and electronic structure
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY, 330:207-219, DEC 15 2012
Amino acid residues affect the formation of backbone fragments upon electron transfer dissociation of doubly charged peptide ions of the AAXAR type. Peptide ions having non-polar residues (X = A, V. L, M, W) undergo backbone dissociations near the protonated N- and C-termini, forming mainly z(1) and z(4) fragment ions. Polar residues (X = H, D) prefer backbone dissociations occurring next to the polar residue, forming z(2) and z(3) fragment ions. Computational analysis, combining molecular dynamics, semi-empirical, density functional theory, and Moller-Plesset theory of precursor ion conformational space, identified the thermodynamically most stable tautomers and conformers for (AAVAR + 2H)(2+), (AAHAR+ 2H)(2+), and (AADAR+ 2H)(2+) precursor ions. Analysis of electronic states and potential energy surfaces for charge-reduced cation-radicals was used to interpret the ETD fragmentations. Electron attachment to (AAVAR + 2H)(2+) and (AAHAR+ 2H)(2+) forms zwitterionic tautomers of charge-reduced cation-radicals as local energy minima in the ground electronic state. These are dynamically unstable with respect to exothermic ammonium proton migration forming aminoketyl intermediates. Direct N-C-alpha, bond cleavage in the zwitterion requires an energy barrier which makes it noncompetitive with the proton migration. This bears on the long-standing chicken-and-egg problem of the ExD dissociation mechanisms according to the Utah-Washington model. Migration of a proton from a proximate neutral amide group was found to form a dynamically unstable enolimidate intermediate that cannot undergo N-C-alpha bond cleavage according to the Murrell-Laidler rule of reaction dynamics. According to electronic structure analysis in a conformationally defined peptide ion, the non-polar side chain in charge-reduced (AAVAR + 2H)(+)* has only a spectator role in isomerizations and backbone dissociations. This casts doubt on the "hydrophobic" effect of amino acid residues on electron-based fragmentations proposed previously. (C) 2012 Elsevier B.V. All rights reserved.
