This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We wish to implement various theoretical methods for the study of fragmentation processes of various classes of biomolecules to complement experimental data, based of tandem MS/MS methods with isotopic labeling and model compounds. We are approaching these problems by using density functional and ab initio calculations as implemented in the Gaussian 03/98 suites of programs for Linux. We have these programs running on two dual/dual-core (quad-processor) installed in this project period and three dual-processor workstation computers and a single-processor workstation computer installed during the previous project period. In addition, Spartan for Linux was installed on the last computer and one of the dual-processor workstations and serves roles in preliminary survey calculations, as graphical interface, and a platform along with Tinker for MD calculations. These current resources facilitate the tackling of larger compounds and more complex processes e.g. unusual generation of radical cations from even-electron precursors. Areas of interest include the fragmentation of (a) modified nucleobases, adducted by polycyclic aromatics hydrocarbons, (b) modified endogenous steroids and sterol-modified nucleobases, and (c) phytosterols (e.g. genistein, luteoline, labdane triterpinoids) and their reactions. These general areas are important for developing analytical methods for cancer biomarkers. Another focus (d) grows from the long-term interest for the Washington University resource in the structural determination of various lipids including phospholipids and their fragmentation in the mass spectrometer. In all of these studies being pursued at the resource, the mechanisms of fragmentation need to be understood to provide a firm foundation for structural studies.
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