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  • Non-covalent complexes of the peptide fragment Gly-Asn-Asn-Gln-Gln-Asn-Tyr in the gas-phase. Photodissociative cross-linking, Born–Oppenheimer molecular dynamics, and ab initio computational binding study
Title: Non-covalent complexes of the peptide fragment Gly-Asn-Asn-Gln-Gln-Asn-Tyr in the gas-phase. Photodissociative cross-linking, Born–Oppenheimer molecular dynamics, and ab initio computational binding study
Non-covalent complexes of the short amyloid peptide motif Gly-Asn-Asn-Gln-Gln-Asn-Tyr (GNNQQNY) with peptide counterparts that were tagged with a diazirine ring at the N-termini (*GNNQQNY) were generated as singly charged ions in the gas phase. Specific laser photodissociation (UVPD) of the diazirine tag in the gas-phase complexes at 355 nm generated transient carbene intermediates that underwent covalent cross-linking with the target GNNQQNY peptide. The crosslinking yields ranged between 0.8 and 4.5%, depending on the combinations of peptide C-terminal amides and carboxylates. The covalent complexes were analyzed by collision-induced dissociation tandem mass spectrometry (CID-MS 3 ), providing distributions of cross-links at the target peptide amino acid residues. A general preference for cross-linking at the target peptide Gln-4-Gln-5-Asn-6-Tyr-7 segment was observed. Born–Oppenheimer molecular dynamics calculations were used to obtain 100 ps trajectories for nine lowest free-energy conformers identified by ωB97X-D/6-31+G(d,p) gradient geometry optimizations. The trajectories were analyzed for close contacts between the incipient carbene atom and the X–H bonds in the target peptide. The close-contact analysis pointed to the Gln-5 and Tyr-7 residues as the most likely sites of cross-linking, consistent with the experimental CID-MS 3 results. Non-covalent binding in the amide complexes was evaluated by DFT calculations of structures and energies. Although antiparallel arrangements of the GNNQQNY and *GNNQQNY peptides were favored in low-energy gas-phase and solvated complexes, the conformations and peptide–peptide interface surfaces were found to differ from the secondary structure of the dry interface in GNNQQNY motifs of amyloid aggregates.  more » « less
Award ID(s):
1661815
PAR ID:
10097159
Author(s) / Creator(s):
; ;
Date Published:
Journal Name:
Physical Chemistry Chemical Physics
Volume:
21
Issue:
4
ISSN:
1463-9076
Page Range / eLocation ID:
2046 to 2056
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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