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Direct Dynamics Simulations of Fragmentation of a Zn(II)-2Cys-2His Oligopeptide. Comparison with Mass Spectrometry Collision-Induced Dissociation
journal contribution
posted on 2019-08-02, 13:04 authored by Abdul Malik, Yu-Fu Lin, Subha Pratihar, Laurence A. Angel, William L. HaseAbnormalities in
zinc metabolism have been linked to many diseases,
including different kinds of cancers and neurological diseases. The
present study investigates the fragmentation pathways of a zinc chaperon
using a model peptide with the sequence acetyl-His1-Cys2-Gly3-Pro4-Tyr5-His6-Cys7 (analog methanobactin peptide-5, amb5). DFT/M05-2X and B3LYP geometry optimizations of [amb5–3H+Zn(II)]− predicted three lowest energy
conformers with different chelating motifs. Direct dynamics simulations,
using the PM7 semiempirical electronic structure method, were performed
for these conformers, labeled a, b, and c, to obtain their fragmentation pathways
at different temperatures in the range 1600–2250 K. The simulation
results were compared with negative ion mode mass spectrometry experiments.
For conformer a, the number of primary dissociation
pathways are 11, 14, 24, 70, and 71 at 1600, 1750, 1875, 2000, and
2250 K, respectively. However, there are only 6, 10, 13, 14, and 19
pathways corresponding to these temperatures that have a probability
of 2% or more. For conformer b, there are 67 pathways
at 2000 K and 71 pathways at 2250 K. For conformer c, 17 pathways were observed at 2000 K. For conformer a, for two of the most common pathways involving C–C bond dissociation,
Arrhenius parameters were calculated. The frequency factors and activation
energies are smaller than those for C–C homolytic dissociation
in alkanes due to increased stability of the product ions as a result
of hydrogen bonding. The activation energies agree with the PM7 barriers
for the C–C dissociations. Comparison of the simulation and
experimental fragmentation ion yields shows the simulations predict
double or triple cleavages of the backbone with Zn(II) retaining its
binding sites, whereas the experiment exhibits single cleavages of
the backbone accompanied by cleavage of two of the Zn(II) binding
sites, resulting in b- and y-type
ions.
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2000 KDirect dynamics simulationsdissociation2250 Kconformerfragmentation ion yieldscleavageDirect Dynamics SimulationsMass Spectrometry Collision-Induced Dissociation Abnormalitiessequence acetyl-His 1DFTZnPM 7 barriersactivation energiesfragmentation pathwaysB 3LYP geometry optimizationsion mode mass spectrometry experiments
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