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Ajax Group. Joshua P. Layfield Jordan C. Vincent Desiree M. Bates Ashley K. Tucker Sara E. Ray Ron C. Estler. Mechanism of Ionization in Matrix-Assisted Laser Desorption Ionization (MALDI): How does proton transfer occur. http://pslc.ws/mactest/maldi.htm. MALDI Overview.
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Ajax Group Joshua P. Layfield Jordan C. Vincent Desiree M. Bates Ashley K. Tucker Sara E. Ray Ron C. Estler Mechanism of Ionization in Matrix-Assisted Laser Desorption Ionization (MALDI): How does proton transfer occur http://pslc.ws/mactest/maldi.htm
MALDI Overview • MALDI is a soft ionization technique that has revolutionized high-molecular weight mass spectrometry • Technique used to measure the molecular weights of a number of systems • Proteins • Polysaccharides • Glyco-lipids • Synthetic Polymers • Nobel Prize Awarded to Fenn and Tanaka in 2002 for the development of soft ionization techniques http://www.magnet.fsu.edu/education /tutorials/tools/ionization_maldi.html
Advantages Used for Disease Diagnosis Able to Ionize Large molecules Accurate / Rapid Analysis Fast Technique Disadvantages Lack of Reproducibility Sample Hot Spots Lack of proper Matrix Molecules Poor Fundamental Understanding of the Mechanism Lack of Rational Design MALDI Overview
Proposed Mechanisms • Cluster Ionization • Ionization occurs after desorption from the matrix • Proton transfer occurs in the gas-phase or in small matrix clusters
Proposed Mechanisms • Photoionzation • Multiple matrix molecule photon absorption • Energy transferred to the analyte in the solid-phase or the gas-phase
Run a MD canonical simulation (CHARMM) to determine the general structure of the matrix protein interactions Optimize the structures of potentially relevant matrix/analyte conformations using electronic structure theory Study the energetics of the proton transfer reactions using intrinsic-reaction-coordinate electronic structure studies for a test set of amino acid/benzoic acid derivatives Methods
Future Challenges • Move beyond pure molecular mechanics • Investigate other possibilities for matrix molecules • Move beyond the gas phase for the MD simulations • Testing new matrix molecules for predictive recommendations to experimentalists