Investigation on gas-phase structures of biomolecules using ion mobility-mass spectrometry /
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| Format: | Thesis eBook |
| Language: | English |
| Published: |
[College Station, Tex.] :
[Texas A&M University],
[2011]
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| Online Access: | Link to OAK Trust copy |
| Abstract: | IM-MS is a 2-D technique which provides separations based on ion shape (ionneutralcollision cross-section, [omega]) and mass (m/z ratio). Ion structures can be deducedfrom the measured collision cross-section ([omega]meas) by calculating the collision crosssections([omega]calc) of candidates generated by molecular dynamics (MD) and compared withthe experiment results. A database of [omega]s for singly-charged peptide ions is presented. Standard proteins are digested using different enzymes (trypsin, chymotrypsin and pepsin), resulting in peptides that differ in amino acid composition. The majority (63%) of the peptide ion correlates well with the globular structures, but some exhibit [omega]s that are significantly larger or smaller than the average correlation. Of the peptide ions having larger [omega]s, approximately 71% are derived from trypsin digestion, and most of the peptide ions that have smaller [omega]s are derived from pepsin digestion, and most of the peptide ions that have smaller [omega]s are deroved from pepson digestion (90%). We use computational simulations and clustering methods to assign backbone conformations for singly-protonated ions of the model peptide (NH₂-Met-Ile-Phe-Ala- Gly-Ile-Lys-COOH) formed by both MALDI and ESI and compare the structures of MIFAGIK derivatives to test the 'sensitivity' of the cluster analysis method. Cluster analysis suggests that [MIFAGIK + H]⁺ ions formed by MALDI have a predominantly turn structure even though the low energy ions prefer partial helical conformers. Although the ions formed by ESI have [omega]s that are different from those formed by MALDI, the results of cluster analysis indicate that the ions backbone structures are similar. Chemical modifications (N-acetyl, methylester, as well as addition of Boc or Fmoc groups) of MIFAGIK, alter the distribution of various conformers. The most dramatic changes are observed for the [M + Na]⁺ ion, which show a strong preference for random coil conformers, owing to the strong solvation by the backbone amide groups. [Omega]meas of oligodeoxynucleotides in different length have been measured in both positive and negative modes. For a given molecular weight and charge state, [omega]meas of the oligodeoxynucleotide, ions are smaller than those of the peptides, indicating their different packing efficiency. A novel generalized non-Boltzman sampling MD has been utilized to investigate the gas-phase ion conformations of dGGATC based on the free energy values. Theory predicts only one low-energy conformer for the zwitterionic form of dGGATC⁻ while dGGATC⁺ ions have several stable conformers in both canonical and zwitterionic form in the gas phase, in good agreement with the experiment. |
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| Item Description: | "Major Subject: Chemistry" Title from author supplied metadata (automated record created 2011-08-09 15:09:44). Electronic resource. |
| Physical Description: | 1 online resource. |
| Bibliography: | Includes bibliographical references. |