COMPUTATIONAL METHODS FOR FRAGMENTATION OF BIOMOLECULES - LIPIDS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们希望实现各种理论方法的研究的各种类别的生物分子的碎片化过程，以补充实验数据，串联MS/MS方法与同位素标记和模型化合物的基础上。我们正在接近这些问题，使用密度泛函和从头计算的高斯03/98套件的程序Linux中实现。我们在本项目期间安装的两台双/双核（四处理器）计算机上运行这些程序，并在上一个项目期间安装了三台双处理器工作站计算机和一台单处理器工作站计算机。 此外，Spartan for Linux安装在最后一台计算机和一个双处理器工作站上，并在初步测量计算中发挥作用，作为图形界面，并与Tinker一起作为沿着平台进行MD计算。这些现有资源有助于处理更大的化合物和更复杂的过程，例如从偶数电子前体中异常生成自由基阳离子。 感兴趣的领域包括（a）被多环芳烃加合的修饰的核碱基，（B）修饰的内源性类固醇和类固醇修饰的核碱基，和（c）植物甾醇（例如染料木黄酮、木犀草素、拉布拉多三萜类化合物）的片段化及其反应。 这些一般领域对于开发癌症生物标志物的分析方法很重要。 另一个焦点（d）来自华盛顿大学对各种脂质（包括磷脂）的结构测定及其在质谱仪中的裂解的长期兴趣。 在所有这些正在进行的资源研究中，需要了解碎片化的机制，为结构研究提供坚实的基础。

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.