From Solution to the Gas Phase: Factors That Influence Kinetic Trapping of Substance P in the Gas Phase

Substance P (RPKPQQFFGLM-NH2) [M + 3H]3+ ions have been shown to exist as two conformers: one that is kinetically trapped and one that is thermodynamically more stable and therefore energetically preferred. Molecular dynamics (MD) simulations suggested that the kinetically trapped population is stab...

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Bibliographic Details
Published in:The journal of physical chemistry. B 2014-12, Vol.118 (49), p.14336-14344
Main Authors: Fort, Kyle L, Silveira, Joshua A, Pierson, Nicholas A, Servage, Kelly A, Clemmer, David E, Russell, David H
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Charge
Gases - chemistry
Glutamine
Ionic mobility
Kinetics
Molecular Conformation
Molecular Dynamics Simulation
Mutations
Phenylalanine
Proline
Simulation
Stabilization
Substance P - analysis
Thermodynamics
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Summary:Substance P (RPKPQQFFGLM-NH2) [M + 3H]3+ ions have been shown to exist as two conformers: one that is kinetically trapped and one that is thermodynamically more stable and therefore energetically preferred. Molecular dynamics (MD) simulations suggested that the kinetically trapped population is stabilized by interactions between the charge sites and the polar side chains of glutamine (Q) located at positions 5 and 6 and phenylalanine (F) located at positions 7 and 8. Here, the individual contributions of these specific intramolecular interactions are systematically probed through site-directed alanine mutations of the native amino acid sequence. Ion mobility spectrometry data for the mutant peptide ions confirm that interactions between the charge sites and glutamine/phenylalanine (Q/F) side chains afford stabilization of the kinetically trapped ion population. In addition, experimental data for proline-to-alanine mutations at positions 2 and 4 clearly show that interactions involving the charge sites and the Q/F side chains are altered by the cis/trans orientations of the proline residues and that mutation of glycine to proline at position 9 supports results from MD simulations suggesting that the C-terminus also provides stabilization of the kinetically trapped conformation.
ISSN:1520-6106
1520-5207
DOI:10.1021/jp5103687