MECHANISTIC STUDY OF ECD OF OLIGOSACCHARIDES

低聚糖ECD机理研究

• 批准号: 8365566
• 负责人: CHI-WEI LIN
• 金额: $ 5.23万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-08-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8365566
• 关键词: Behavior; Binding; Binding Sites; Biological Models; Biology; Boston; Calcium; Cations; Code; Complex; Dissociation; Electrons; Funding; Grant; Ions; Isomerism; Mass Spectrum Analysis; Medicine; Metal Binding Site; Metals; Methods; Modeling; Molecular Conformation; National Center for Research Resources; Oligosaccharides; Oxygen; Pattern; Principal Investigator; Process; Research; Research Infrastructure; Resources; Sampling; Source; Supercomputing; System; Techniques; Theoretical Studies; United States National Institutes of Health; Universities; Update; Variant; base; conformer; cost; density; design; flexibility; metal complex; molecular dynamics; molecular orbital; quantum chemistry; software development; theories; tool

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. This theoretical study is aimed at explaining the fragmentation behavior of various oligosaccharide-metal complex ions, under electron capture dissociation (ECD) conditions. A better understanding of the fragmentation mechanism will help to establish a reliable mass spectrometric method for structural characterization of oligosaccharides. Due to the isomeric complexity and the large size of oligosaccharides, direct theoretical approach to the ECD process of actual oligosaccharide systems from first principle is practically forbidden. Currently, the research is carried out in two aspects: 1) The determination of the energetically preferred metal-binding sites for oligosaccharides, using molecular dynamics (MD) simulation techniques. Since electron capture is likely to occur near the metal cation, the ECD fragmentation pattern is expected to be heavily influenced by the metal-binding sites. MD simulation is a useful tool to perform conformation space sampling of large flexible biomolecules. In this study, MD simulation was performed by applying the CHARMm force field, using the Discovery Studio software developed by Accelrys. We have identified some low energy conformers for the maltohexaose-Ca2+ complex, where the calcium cation is bound to several spatially adjacent oxygen or CH2OH group. Binding-site variations in linkage and epimeric/anomeric isomers are currently being investigated. 2) The mechanistic study of ECD of model oligosaccharide systems. Based on the ECD results and MD simulation determined metal-oligosaccharide binding sites, model systems representing actual oligosaccharide-metal complexes will be designed and the high level ab initio- and density functional theory-based molecular orbital calculations will be performed to elucidate the ECD mechanism. These calculations will be carried out using Gaussian 03 quantum chemistry codes, utilizing the supercomputing facilities of Boston University (IBM pSeries Cluster and IBM BladeCenter). Update for the 2010-2011 period can be found in the subproject progress section.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 本理论研究旨在解释电子捕获解离（ECD）条件下各种寡糖-金属络离子的碎裂行为。更好地理解断裂机制将有助于建立可靠的寡糖结构表征的质谱方法。 由于寡糖异构体的复杂性和大尺寸，从第一原理直接理论研究实际寡糖系统的 ECD 过程实际上是被禁止的。目前，研究工作主要分为两方面： 1) 使用分子动力学 (MD) 模拟技术确定寡糖的能量首选金属结合位点。 由于电子捕获很可能发生在金属阳离子附近，因此 ECD 碎片模式预计会受到金属结合位点的严重影响。 MD 模拟是对大型柔性生物分子进行构象空间采样的有用工具。在本研究中，MD 模拟是通过使用 Accelrys 开发的 Discovery Studio 软件应用 CHARMm 力场来进行的。我们已经确定了麦芽六糖-Ca2+复合物的一些低能构象异构体，其中钙阳离子与几个空间相邻的氧或CH2OH基团结合。目前正在研究连接和差向异构体/端基异构体的结合位点变化。 2）模型寡糖系统的ECD机理研究。 根据 ECD 结果和 MD 模拟确定的金属-寡糖结合位点，将设计代表实际寡糖-金属复合物的模型系统，并进行基于高水平从头算和密度泛函理论的分子轨道计算，以阐明 ECD 机制。 这些计算将使用 Gaussian 03 量子化学代码并利用波士顿大学的超级计算设施（IBM pSeries Cluster 和 IBM BladeCenter）进行。 2010-2011 年期间的更新信息可在子项目进展部分找到。