COMPUTATIONAL METHODS FOR FRAGMENTATION OF BIOMOLECULES - LIPIDS

生物分子断裂的计算方法 - 脂质

• 批准号: 8361318
• 负责人: MICHAEL L GROSS
• 金额: $ 0.79万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361318
• 关键词: Area; Aromatic Polycyclic Hydrocarbons; Biological Markers; Cations; Complement; Complex; Computer Workstations; Computers; Computing Methodologies; Databases; Electrons; Foundations; Funding; Generations; Genistein; Grant; Labdanes; Label; Linux; Lipid A; Lipids; Luteolin; Malignant Neoplasms; Mass Spectrum Analysis; Methods; Modeling; National Center for Research Resources; Phospholipids; Phytosterols; Principal Investigator; Process; Reaction; Research; Research Infrastructure; Resources; Role; Running; Source; Steroids; Sterols; Surveys; United States National Institutes of Health; Universities; Washington; adduct; analytical method; biomedical resource; cost; density; graphical user interface; interest; mass spectrometer; programs

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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 我们希望实施各种理论方法，以研究各种生物分子的碎裂过程，以补充具有同位素标记和模型化合物的串联MS/MS方法的实验数据。我们正在通过使用高斯03/98 Linux程序套件中实现的密度功能和从头算计算来解决这些问题。我们将这些程序运行在本项目期间安装的两个双/双核（Quad Parocessor），以及三台双处理器工作站计算机和上一个项目期间安装的单处理器工作站计算机。 此外，Linux的Spartan安装在最后一台计算机和双处理器工作站之一上，并在初步调查计算中扮演角色，作为图形接口，以及用于MD计算的Tinker以及平台。这些当前的资源有助于解决较大的化合物和更复杂的过程，例如从偶数前体产生了激进阳离子的异常产生。 感兴趣的领域包括（a）修饰的核仁酶的碎片，由多环芳烃碳氢化合物加入，（b）改良的内源性类固醇和固醇修饰的核碱基，以及（c）植物固醇（例如，基因碱基，luteoline，luteoline，labdane trertrinetoips）及其反应。 这些一般领域对于开发用于癌症生物标志物的分析方法很重要。 另一个重点（d）源自华盛顿大学资源的长期兴趣，以确定包括磷脂在内的各种脂质及其在质谱仪中的破碎。 在所有这些研究中，都需要理解分裂的机制，以为结构研究提供坚定的基础。